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Sample records for human herpesvirus 6a

  1. LYMPHOPROLIFERATIVE SYNDROMES ASSOCIATED WITH HUMAN HERPESVIRUS-6A AND HUMAN HERPESVIRUS-6B

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    Eva Eliassen

    2018-05-01

    Full Text Available Human herpesvirus 6A and 6B (HHV-6A and HHV-6B have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS, and nodular sclerosis Hodgkin’s lymphoma. Herein, we discuss the conditions associated with the lymphoproliferative capacity of HHV-6, as well as the potential mechanisms behind them. Continued exploration on this topic may add to our understanding of the interactions between HHV-6 and the immune system and may open the doors to more accurate diagnosis and treatment of certain lymphoproliferative disorders.

  2. Complexities in human herpesvirus-6A and -6B binding to host cells

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    Pedersen, Simon Metz; Höllsberg, Per

    2006-01-01

    Human herpesvirus-6A and -6B uses the cellular receptor CD46 for fusion and infection of the host cell. The viral glycoprotein complex gH-gL from HHV-6A binds to the short consensus repeat 2 and 3 in CD46. Although all the major isoforms of CD46 bind the virus, certain isoforms may have higher...

  3. Human herpesvirus-6A/B binds to spermatozoa acrosome and is the most prevalent herpesvirus in semen from sperm donors

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    Kaspersen, Maja Døvling; Larsen, Peter B.; Kofod-Olsen, Emil

    2012-01-01

    An analysis of all known human herpesviruses has not previously been reported on sperm from normal donors. Using an array-based detection method, we determined the cross-sectional frequency of human herpesviruses in semen from 198 Danish sperm donors. Fifty-five of the donors had at least one...... ejaculate that was positive for one or more human herpesvirus. Of these 27.3% (n = 15) had a double herpesvirus infection. If corrected for the presence of multiple ejaculates from some donors, the adjusted frequency of herpesviruses in semen was 27.2% with HSV-1 in 0.4%; HSV-2 in 0.1%; EBV in 6.3%; HCMV...... not necessarily remain positive over time. For the most frequently found herpesvirus, HHV-6A/B, we examined its association with sperm. For HHV-6A/B PCR-positive semen samples, HHV-6A/B could be detected on the sperm by flow cytometry. Conversely, PCR-negative semen samples were negative by flow cytometry. HHV-6B...

  4. The Neutralizing Linear Epitope of Human Herpesvirus 6A Glycoprotein B Does Not Affect Virus Infectivity.

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    Wakata, Aika; Kanemoto, Satoshi; Tang, Huamin; Kawabata, Akiko; Nishimura, Mitsuhiro; Jasirwan, Chyntia; Mahmoud, Nora Fahmy; Mori, Yasuko

    2018-03-01

    Human herpesvirus 6A (HHV-6A) glycoprotein B (gB) is a glycoprotein consisting of 830 amino acids and is essential for the growth of the virus. Previously, we reported that a neutralizing monoclonal antibody (MAb) called 87-y-13 specifically reacts with HHV-6A gB, and we identified its epitope residue at asparagine (Asn) 347 on gB. In this study, we examined whether the epitope recognized by the neutralizing MAb is essential for HHV-6A infection. We constructed HHV-6A bacterial artificial chromosome (BAC) genomes harboring substitutions at Asn347, namely, HHV-6A BACgB(N347K) and HHV-6A BACgB(N347A). These mutant viruses could be reconstituted and propagated in the same manner as the wild type and their revertants, and MAb 87-y-13 could not inhibit infection by either mutant. In a cell-cell fusion assay, Asn at position 347 on gB was found to be nonessential for cell-cell fusion. In addition, in building an HHV-6A gB homology model, we found that the epitope of the neutralizing MAb is located on domain II of gB and is accessible to solvents. These results indicate that Asn at position 347, the linear epitope of the neutralizing MAb, does not affect HHV-6A infectivity. IMPORTANCE Glycoprotein B (gB) is one of the most conserved glycoproteins among all herpesviruses and is a key factor for virus entry. Therefore, antibodies targeted to gB may neutralize virus entry. Human herpesvirus 6A (HHV-6A) encodes gB, which is translated to a protein of about 830 amino acids (aa). Using a monoclonal antibody (MAb) for HHV-6A gB, which has a neutralizing linear epitope, we analyzed the role of its epitope residue, N347, in HHV-6A infectivity. Interestingly, this gB linear epitope residue, N347, was not essential for HHV-6A growth. By constructing a homology model of HHV-6A gB, we found that N347 was located in the region corresponding to domain II. Therefore, with regard to its neutralizing activity against HHV-6A infection, the epitope on gB might be exposed to solvents

  5. Purification of infectious human herpesvirus 6A virions and association of host cell proteins

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    Garoff Henrik

    2007-10-01

    Full Text Available Abstract Background Viruses that are incorporating host cell proteins might trigger autoimmune diseases. It is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6A (HHV-6A in multiple sclerosis (MS. Results We have established a method for rapid and morphology preserving purification of HHV-6A virions, which in combination with parallel analyses with background control material released from mock-infected cells facilitates qualitative and quantitative investigations of the protein content of HHV-6A virions. In our iodixanol gradient purified preparation, we detected high levels of viral DNA by real-time PCR and viral proteins by metabolic labelling, silver staining and western blots. In contrast, the background level of cellular contamination was low in the purified samples as demonstrated by the silver staining and metabolic labelling analyses. Western blot analyses showed that the cellular complement protein CD46, the receptor for HHV-6A, is associated with the purified and infectious virions. Also, the cellular proteins clathrin, ezrin and Tsg101 are associated with intact HHV-6A virions. Conclusion Cellular proteins are associated with HHV-6A virions. The relevance of the association in disease and especially in autoimmunity will be further investigated.

  6. Complexities in human herpesvirus-6A and -6B binding to host cells

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    Pedersen, Simon Metz; Hoellsberg, Per

    2006-01-01

    Human herpesvirus-6A and -6B uses the cellular receptor CD46 for fusion and infection of the host cell. The viral glycoprotein complex gH-gL from HHV-6A binds to the short consensus repeat 2 and 3 in CD46. Although all the major isoforms of CD46 bind the virus, certain isoforms may have higher affinity than others for the virus. Within recent years, elucidation of the viral complex has identified additional HHV-6A and -6B specific glycoproteins. Thus, gH-gL associates with a gQ1-gQ2 dimer to form a heterotetrameric complex. In addition, a novel complex consisting of gH-gL-gO has been described that does not bind CD46. Accumulating evidence suggests that an additional HHV-6A and -6B receptor exists. The previous simple picture of HHV-6A/B-host cell contact therefore includes more layers of complexities on both the viral and the host cell side of the interaction

  7. Cell Culture Systems To Study Human Herpesvirus 6A/B Chromosomal Integration.

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    Gravel, Annie; Dubuc, Isabelle; Wallaschek, Nina; Gilbert-Girard, Shella; Collin, Vanessa; Hall-Sedlak, Ruth; Jerome, Keith R; Mori, Yasuko; Carbonneau, Julie; Boivin, Guy; Kaufer, Benedikt B; Flamand, Louis

    2017-07-15

    Human herpesviruses 6A/B (HHV-6A/B) can integrate their viral genomes in the telomeres of human chromosomes. The viral and cellular factors contributing to HHV-6A/B integration remain largely unknown, mostly due to the lack of efficient and reproducible cell culture models to study HHV-6A/B integration. In this study, we characterized the HHV-6A/B integration efficiencies in several human cell lines using two different approaches. First, after a short-term infection (5 h), cells were processed for single-cell cloning and analyzed for chromosomally integrated HHV-6A/B (ciHHV-6A/B). Second, cells were infected with HHV-6A/B and allowed to grow in bulk for 4 weeks or longer and then analyzed for the presence of ciHHV-6. Using quantitative PCR (qPCR), droplet digital PCR, and fluorescent in situ hybridization, we could demonstrate that HHV-6A/B integrated in most human cell lines tested, including telomerase-positive (HeLa, MCF-7, HCT-116, and HEK293T) and telomerase-negative cell lines (U2OS and GM847). Our results also indicate that inhibition of DNA replication, using phosphonoacetic acid, did not affect HHV-6A/B integration. Certain clones harboring ciHHV-6A/B spontaneously express viral genes and proteins. Treatment of cells with phorbol ester or histone deacetylase inhibitors triggered the expression of many viral genes, including U39 , U90 , and U100 , without the production of infectious virus, suggesting that the tested stimuli were not sufficient to trigger full reactivation. In summary, both integration models yielded comparable results and should enable the identification of viral and cellular factors contributing to HHV-6A/B integration and the screening of drugs influencing viral gene expression, as well as the release of infectious HHV-6A/B from the integrated state. IMPORTANCE The analysis and understanding of HHV-6A/B genome integration into host DNA is currently limited due to the lack of reproducible and efficient viral integration systems. In the

  8. Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration.

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    Gilbert-Girard, Shella; Gravel, Annie; Artusi, Sara; Richter, Sara N; Wallaschek, Nina; Kaufer, Benedikt B; Flamand, Louis

    2017-07-15

    Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency ( P integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A. IMPORTANCE HHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3' extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the

  9. Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

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    Gu Bin

    2011-12-01

    Full Text Available Abstract Background Human herpesvirus 6 (HHV-6 is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs during productive HHV-6A infection and the underlying mechanisms. Results HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP, which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs. Conclusion This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

  10. Novel marmoset (Callithrix jacchus model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization.

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    Emily Leibovitch

    2013-01-01

    Full Text Available Human Herpesvirus 6 (HHV-6 is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

  11. Summary of the 10th International Conference on Human Herpesviruses-6 and -7 (HHV-6A, -6B, and HHV-7).

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    Komaroff, Anthony L; Boeckh, Michael; Eliason, Eva; Phan, Tuan; Kaufer, Benedikt B

    2018-04-01

    The 10th International Conference on Human herpesviruses-6 and -7 (HHV-6A, HHV-6B, and HHV-7) was held at the Freie Universität, Berlin, Germany from July 23-26, 2017. It attracted more than 130 basic, translational and clinical scientists from 19 countries. Important new information was presented regarding: the biology of HHV-6A and -6B; the biology and epidemiology of inherited chromosomally integrated HHV-6A and -6B; improved diagnostic tests; animal models for and animal viruses with similarities to HHV-6A, -6B, and -7; established and possible disease associations; and new treatment strategies. Here, we summarize work presented at the meeting that is of particular interest. © 2017 Wiley Periodicals, Inc.

  12. Activation of human herpesvirus replication by apoptosis.

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    Prasad, Alka; Remick, Jill; Zeichner, Steven L

    2013-10-01

    A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

  13. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

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    Tweedy, J; Spyrou, MA; Pearson, M; Lassner, D; Kuhl, U; Gompels, UA

    2016-01-01

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, imp...

  14. Analyses of Tissue Culture Adaptation of Human Herpesvirus-6A by Whole Genome Deep Sequencing Redefines the Reference Sequence and Identifies Virus Entry Complex Changes.

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    Tweedy, Joshua G; Escriva, Eric; Topf, Maya; Gompels, Ursula A

    2017-12-31

    Tissue-culture adaptation of viruses can modulate infection. Laboratory passage and bacterial artificial chromosome (BAC)mid cloning of human cytomegalovirus, HCMV, resulted in genomic deletions and rearrangements altering genes encoding the virus entry complex, which affected cellular tropism, virulence, and vaccine development. Here, we analyse these effects on the reference genome for related betaherpesviruses, Roseolovirus, human herpesvirus 6A (HHV-6A) strain U1102. This virus is also naturally "cloned" by germline subtelomeric chromosomal-integration in approximately 1% of human populations, and accurate references are key to understanding pathological relationships between exogenous and endogenous virus. Using whole genome next-generation deep-sequencing Illumina-based methods, we compared the original isolate to tissue-culture passaged and the BACmid-cloned virus. This re-defined the reference genome showing 32 corrections and 5 polymorphisms. Furthermore, minor variant analyses of passaged and BACmid virus identified emerging populations of a further 32 single nucleotide polymorphisms (SNPs) in 10 loci, half non-synonymous indicating cell-culture selection. Analyses of the BAC-virus genome showed deletion of the BAC cassette via loxP recombination removing green fluorescent protein (GFP)-based selection. As shown for HCMV culture effects, select HHV-6A SNPs mapped to genes encoding mediators of virus cellular entry, including virus envelope glycoprotein genes gB and the gH/gL complex. Comparative models suggest stabilisation of the post-fusion conformation. These SNPs are essential to consider in vaccine-design, antimicrobial-resistance, and pathogenesis.

  15. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

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    Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A

    2016-01-15

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

  16. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

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    Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A.

    2016-01-01

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. PMID:26784220

  17. Human herpesviruses and MS

    DEFF Research Database (Denmark)

    Christensen, Tove

    2007-01-01

    and they are capable of reactivation. Epstein Barr virus (EBV), HHV-6A and varicella zoster virus (VZV) are consistently linked with MS, particularly with respect to epidemiology, antibody responses in serum (EBV) and cerebrospinal fluid (EBV and HHV-6A), and with MS exacerbations that are associated with viral...... reactivation (VZV, HHV-6A and EBV). HHV have the potential for a causal role in MS--they may be key players in the disease process--and this role could be mediated through several direct or indirect mechanisms....

  18. PREVALENCE OF INFECTION WITH HUMAN HERPESVIRUS ...

    African Journals Online (AJOL)

    human herpesvirus 8 (HHV 8): Distribution of infection in Kaposi's sarcoma risk groups and evidence of sexual transmission. Nat Med 1996; 2: 918-924. 14. Kedes OH, Ganem 0, Ameli N, Bacchetti p. Greenblatt R The prevalence of serum antibody to human herpesvirus 8 (Kaposi sarcoma-associated hepesvirus) among ...

  19. A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.

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    Patel, Swapneel J; Zhao, Guoyan; Penna, Vinay R; Park, Eugene; Lauron, Elvin J; Harvey, Ian B; Beatty, Wandy L; Plougastel-Douglas, Beatrice; Poursine-Laurent, Jennifer; Fremont, Daved H; Wang, David; Yokoyama, Wayne M

    2017-05-01

    The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 + T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7. IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and

  20. Human herpesvirus 8 – A novel human pathogen

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    Edelman Daniel C

    2005-09-01

    Full Text Available Abstract In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8 1. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.

  1. Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

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    Watanabe, Takahiro; Kawamura, Tatsuyoshi; Jacob, Sharon E; Aquilino, Elisabeth A; Orenstein, Jan M; Black, Jodi B; Blauvelt, Andrew

    2002-10-01

    Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

  2. Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

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    Bonnafous, Pascale; Gautheret-Dejean, Agnès

    2015-01-01

    SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and

  3. Structure of replicating intermediates of human herpesvirus type 6

    International Nuclear Information System (INIS)

    Severini, Alberto; Sevenhuysen, Claire; Garbutt, Michael; Tipples, Graham A.

    2003-01-01

    We have studied the structure of the replicative intermediates of human herpesvirus 6 (HHV-6) using pulsed-field gel electrophoresis, partial digestion, two-dimensional gel electrophoresis, and sedimentation centrifugation. The results show that DNA replication of HHV-6 produces head-to-tail concatemeric intermediates as well as approximately equal amounts of circular monomers or oligomers. Unlike the situation in herpes simplex virus, the intermediates of human herpesvirus 6 replication are not highly branched, suggesting a difference in the mechanism of replication or a lower frequency of homologous recombination in human herpesvirus 6 compared to herpes simplex virus

  4. Induction of cell-cell fusion from without by human herpesvirus 6B

    DEFF Research Database (Denmark)

    Pedersen, Simon Metz; Øster, Bodil; Bundgaard, Bettina

    2006-01-01

    Human herpesvirus (HHV) 6A induce fusion from without (FFWO), whereas HHV-6B is believed to be ineffective in this process. Here, we demonstrate that HHV-6B induces rapid fusion in both epithelial cells and lymphocytes. The fusion was identified 1 h postinfection, could be inhibited by antibodies...

  5. Human Herpesvirus 6 and Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Daniel Eymard

    1993-01-01

    Full Text Available The cause of chronic fatigue syndrome (CFS is still enigmatic. Using indirect immunofluorescence testing for measuring antibody against human herpesvirus 6 (HHV-6, this study investigated the association of CFS with infection by HHV-6. Seventeen patients (group A fulfilling the Centers for Disease Control (CDC definition for CFS were compared with eight patients (group B with chronic fatigue but not meeting the CDC criteria. No significant difference was found between the two groups for 30 parameters including sex, age, exposure to children and serology for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and toxoplasma. Univariate analysis showed that patients in group A complained more frequently of a sore throat, headache and of recurrent type of fatigue. These three parameters are discriminant in identifying patients who will meet the CDC case definition of CFS. The titre of antibody against HHV-6 in group A (1:99 was significantly higher than in group B (1:15 (P=0.007. Elevated HHV-6 titres suggests that this virus could be a cofactor in the pathogenesis of CFS.

  6. Restriction of human herpesvirus 6B replication by p53

    DEFF Research Database (Denmark)

    Øster, Bodil; Kofod-Olsen, Emil; Bundgaard, Bettina

    2008-01-01

    Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53...

  7. Differential activation of murine herpesvirus 68- and Kaposi's sarcoma-associated herpesvirus-encoded ORF74 G protein-coupled receptors by human and murine chemokines

    NARCIS (Netherlands)

    Verzijl, D.; Fitzsimons, C.P.; Van Dijk, M.; Stewart, J.P.; Timmerman, H.; Smit, M.J.; Leurs, R.

    2004-01-01

    Infection of mice with murine gammaherpesvirus 68 (MHV-68) is a well-characterized small animal model for the study of gammaherpesvirus infection. MHV-68 belongs to the same herpesvirus family as herpesvirus saimiri (HVS) of New World squirrel monkeys and human herpesvirus 8 (HHV-8) (also referred

  8. Association of human herpesvirus 6 subtypes with symptomatic apical periodontitis.

    Science.gov (United States)

    Hernádi, Katinka; Csoma, Eszter; Adám, Balázs; Szalmás, Anita; Gyöngyösi, Eszter; Veress, György; Ildikó-Márton; Kónya, József

    2011-09-01

    The occurrence of human herpesvirus (HHV) 6 subtypes A and B in apical periodontitis was determined. The relationship of HHV-6 subtypes to other disease associated herpesviruses, i.e., Epstein-Barr virus (EBV) and human cytomegalovirus, was also investigated. Forty apical periodontitis samples (17 symptomatic and 23 asymptomatic) and 40 healthy pulp control samples were collected. Nested polymerase chain reaction was used to detect HHV-6 DNA. HHV-6 DNA was observed in significantly higher frequencies in apical periodontitis samples than in control samples (20% vs. 2.5%; P = .03). Further classification of apical lesions revealed that subtype B of HHV-6 was significantly associated with large-sized and symptomatic lesions (P apical lesions (77%) harbored ≥1 of the tested herpesviruses: EBV was the most frequent herpesvirus (72.5%) in apical periodontitis, followed by HHV-6 (20%). Our findings suggest that EBV and HHV-6B infections can be associated with symptomatic apical periodontitis. Copyright © 2011 Mosby, Inc. All rights reserved.

  9. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health.

    Science.gov (United States)

    Wood, Michael L; Royle, Nicola J

    2017-07-12

    Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease.

  10. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  11. Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

    Directory of Open Access Journals (Sweden)

    Jessica M Hogestyn

    2018-01-01

    Full Text Available Human herpesviruses (HVs have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS. The ability of HVs to enter a state of latency, a defining characteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease (NDD pathology by highlighting two prominent members of the HV family, herpes simplex virus 1 (HSV-1 and human herpesvirus 6 (HHV-6. We (i introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then (ii review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer's disease (AD and multiple sclerosis (MS, respectively. We then (iii highlight and discuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we (iv discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

  12. Human herpesvirus-6 and -7 DNA in cerebrospinal fluid of facial palsy patients.

    Science.gov (United States)

    Kanerva, Mervi; Jääskeläinen, Anne J; Suvela, Minna; Piiparinen, Heli; Vaheri, Antti; Pitkäranta, Anne

    2008-04-01

    Finding human herpesvirus (HHV)-7 and dual HHV-6A and -6B DNA in cerebrospinal fluid (CSF) of two facial palsy (FP) patients is intriguing but does not allow etiologic conclusions as such. HHV-6 or -7 DNA was revealed in 10% of the CSF samples tested from 70 immunocompetent adolescents and adults; a highly unusual result. How these findings are associated with the diseases they accompany remains to be defined. To determine whether herpes simplex virus (HSV)-1 and -2, varicella-zoster virus (VZV), HHV-6A, -6B, and -7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) DNA could be found in CSF of FP patients or controls. In all, 33 peripheral FP patients (26 idiopathic, 5 with herpesvirus infection, 1 puerperal, 1 Melkersson-Rosenthal syndrome) (34 CSF samples) and 36 controls (16 nonidiopathic FP, 7 hearing loss, 6 vertigo, 5 headache, 2 other) previously tested for HSV-1, VZV, and HHV-6 DNA by polymerase chain reaction (PCR) were tested with highly sensitive multiplex-PCR and an oligonucleotide microarray method. One FP patient had HHV-7 DNA and another had HHV-6A and -6B DNA simultaneously. In the control group, one HHV-7, one HHV-6A, and three HHV-6B DNA-positive specimens were found.

  13. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

    Science.gov (United States)

    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

  14. Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes.

    Science.gov (United States)

    Ericsson, Maja; Skog, Oskar

    The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.

  15. Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution.

    Science.gov (United States)

    Renner, Daniel W; Szpara, Moriah L

    2018-01-01

    Until fairly recently, genome-wide evolutionary dynamics and within-host diversity were more commonly examined in the context of small viruses than in the context of large double-stranded DNA viruses such as herpesviruses. The high mutation rates and more compact genomes of RNA viruses have inspired the investigation of population dynamics for these species, and recent data now suggest that herpesviruses might also be considered candidates for population modeling. High-throughput sequencing (HTS) and bioinformatics have expanded our understanding of herpesviruses through genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures. Here we discuss recent data on the mechanisms that generate herpesvirus genomic diversity and underlie the evolution of these virus families. We focus on human herpesviruses, with key insights drawn from veterinary herpesviruses and other large DNA virus families. We consider the impacts of cell culture on herpesvirus genomes and how to accurately describe the viral populations under study. The need for a strong foundation of high-quality genomes is also discussed, since it underlies all secondary genomic analyses such as RNA sequencing (RNA-Seq), chromatin immunoprecipitation, and ribosome profiling. Areas where we foresee future progress, such as the linking of viral genetic differences to phenotypic or clinical outcomes, are highlighted as well. Copyright © 2017 Renner and Szpara.

  16. Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution

    Science.gov (United States)

    Renner, Daniel W.

    2017-01-01

    ABSTRACT Until fairly recently, genome-wide evolutionary dynamics and within-host diversity were more commonly examined in the context of small viruses than in the context of large double-stranded DNA viruses such as herpesviruses. The high mutation rates and more compact genomes of RNA viruses have inspired the investigation of population dynamics for these species, and recent data now suggest that herpesviruses might also be considered candidates for population modeling. High-throughput sequencing (HTS) and bioinformatics have expanded our understanding of herpesviruses through genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures. Here we discuss recent data on the mechanisms that generate herpesvirus genomic diversity and underlie the evolution of these virus families. We focus on human herpesviruses, with key insights drawn from veterinary herpesviruses and other large DNA virus families. We consider the impacts of cell culture on herpesvirus genomes and how to accurately describe the viral populations under study. The need for a strong foundation of high-quality genomes is also discussed, since it underlies all secondary genomic analyses such as RNA sequencing (RNA-Seq), chromatin immunoprecipitation, and ribosome profiling. Areas where we foresee future progress, such as the linking of viral genetic differences to phenotypic or clinical outcomes, are highlighted as well. PMID:29046445

  17. Prevalence of infection with human herpesvirus 8/Kaposi's sarcoma ...

    African Journals Online (AJOL)

    8)/Kaposi's sarcoma herpesvirus (KSHY) and to gain some insight into possible transmission dynamics of this novel virus in South Africa. Methods. Stored, anonymous serum from 50 patients with a ~ sexually transmitted disease (STD), ...

  18. Human herpesviruses respiratory infections in patients with acute respiratory distress (ARDS).

    Science.gov (United States)

    Bonizzoli, Manuela; Arvia, Rosaria; di Valvasone, Simona; Liotta, Francesco; Zakrzewska, Krystyna; Azzi, Alberta; Peris, Adriano

    2016-08-01

    Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype.

  19. [Studies on the novel association of human herpesvirus-7 with skin diseases].

    Science.gov (United States)

    Vág, Tibor; Sonkoly, Enikó; Kemény, Béla; Kárpáti, Sarolta; Horváth, Attila; Ongrádi, József

    2003-08-17

    Human herpesvirus 7 in pityriasis rosea, this and other viruses in papular-purpuric gloves-and-socks syndrome have been implicated, but their primary or recurrent infections are still in question. In one available blood sample, therefore, IgM, IgG and its high avidity fraction characteristic for recurrent infections were quantitated by indirect immunofluorescence. Peripheral lymphocytes were subjected to nested polymerase chain reaction to detect viral DNA, or cocultivated with several cell cultures. One third of 33 pityriasis rosea patients had elevated IgM, another third had elevated IgG without high avidity molecules to human herpesvirus 7 suggesting primary infection. Thirty percent of controls, more than half of the patients had virtual DNA in their lymphocytes, but only one in 5 skin biopsy specimens were PCR positive. All three co-cultivation attempts yielded viruses extremely rapidly, verified by electron microscopy, polymerase chain reaction and monoclonal antibodies as human herpesvirus 7. These are the first isolates in the geographical regions of Hungary. These data suggest that pityriasis rosea is the consequence of a primary human herpesvirus 7 infection in seronegative adults, and only occasionally is due to virus reactivation. One patient with gloves-and-socks syndrome had an acute, another patient had a persistent coinfection with human herpesvirus 7 and parvovirus B19, two others had a primary herpesvirus 7 infection. Interestingly, this disease might be elicited by both viruses individually or in synergism. Neither human herpesvirus 7 nor parvovirus B19 infect skin cells, but both can be detected in the infiltrating lymphocytes of skin eruptions, in which they induce an altered mediator production, that might be responsible for the general and local symptoms.

  20. Prevalence of human herpesvirus 8 infection in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Sun Shipeng

    2011-05-01

    Full Text Available Abstract Background For decades, scientists have tried to understand the environmental factors involved in the development of systemic lupus erythematosus (SLE, in which viral infections was included. Previous studies have identified Epstein-Barr virus (EBV to incite SLE. Human herpesvirus 8 (HHV-8, another member of the gammaherpesvirus family, shares a lot in common with EBV. The characteristics of HHV-8 make it a well-suited candidate to trigger SLE. Results In the present study, serum samples from patients (n = 108 with diagnosed SLE and matched controls (n = 122 were collected, and the prevalence of HHV-8 was compared by a virus-specific nested PCR and a whole virus enzyme-linked immunoassay (EIA. There was significant difference in the prevalence of HHV-8 DNA between SLE patients and healthy controls (11 of 107 vs 1 of 122, p = 0.001; significant difference was also found in the detection of HHV-8 antibodies (19 of 107 vs 2 of 122, p We also detected the antibodies to Epstein-Barr virus viral capsid antigen (EBV-VCA and Epstein-Barr nuclear antigen-1 (EBNA-1. Both patients and controls showed high seroprevalence with no significant difference (106 of 107 vs 119 of 122, p = 0.625. Conclusion Our finding indicated that there might be an association between HHV-8 and the development of SLE.

  1. Association of classic lichen planus with human herpesvirus-7 infection.

    Science.gov (United States)

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Ghazvini, Kiarash; Esmaily, Habibollah; Esmaeelzadeh, Maryam

    2017-01-01

    Lichen planus is a mucocutaneous papulosquamous itchy disease with unknown etiology. A number of factors such as immune mechanisms, viral agents, and drugs have been implicated in pathogenesis of lichen planus. In recent years, several studies have indicated the role of viral agents in this disease, including human herpesvirus-7 (HHV-7). Studies have given contradictory results, which is why we decided to study the possible association between lichen planus with HHV-7. In this case-control study, which was conducted on 60 cutaneous classic lichen planus samples as well as 60 healthy control skin samples after matching the two groups in terms of gender and age, tissue samples of patients and controls were studied by real time polymerase chain reaction to detect for HHV-7. According to this study, HHV-7 DNA was found in 18 samples of the case group (30.0%) and in six (10.0%) of the control group (P = 0.006). The results of this study support the likely role of HHV-7 in pathogenesis of lichen planus. As an exogenous antigen, this virus may be involved in cellular immune-mediated destruction of keratinocytes. © 2016 The International Society of Dermatology.

  2. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    The chemokine-like, secreted protein product of the U83 gene from human herpesvirus 6, here named vCCL4, was chemically synthesized to be characterized in a complete library of the 18 known human chemokine receptors expressed individually in stably transfected cell lines. vCCL4 was found to cause...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  3. Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates?

    NARCIS (Netherlands)

    Greensill, J.; Sheldon, J. A.; Renwick, N. M.; Beer, B. E.; Norley, S.; Goudsmit, J.; Schulz, T. F.

    2000-01-01

    Primate gamma-2 herpesviruses (rhadinoviruses) have so far been found in humans (Kaposi's sarcoma-associated herpesvirus [KSHV], also called human herpesvirus 8), macaques (Macaca spp.) (rhesus rhadinovirus [RRV] and retroperitoneal fibromatosis herpesvirus [RFHV]), squirrel monkeys (Saimiri

  4. Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

    NARCIS (Netherlands)

    Renwick, N.; Halaby, T.; Weverling, G. J.; Dukers, N. H.; Simpson, G. R.; Coutinho, R. A.; Lange, J. M.; Schulz, T. F.; Goudsmit, J.

    1998-01-01

    The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. The Amsterdam Cohort Studies on HIV infection and AIDS

  5. Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway

    DEFF Research Database (Denmark)

    Øster, Bodil; Kaspersen, M.D.; Kofod-Olsen, Emil

    2006-01-01

    BACKGROUND: Various forms of cellular stress can activate the tumour suppressor protein p53, an important regulator of cell cycle arrest, apoptosis, and cellular senescence. Cells infected by human herpesvirus 6B (HHV-6B) accumulate aberrant amounts of p53. OBJECTIVES: The aim of this study...

  6. Identification of proteins specific for human herpesvirus 6-infected human T cells

    International Nuclear Information System (INIS)

    Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

    1989-01-01

    Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpesviruses reacted with fewer HHV-6-infected cell proteins, and only a 135,000-M r polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105k and gp82k, gp116k, gp64k, and gp54k, and gp102k

  7. JST Thesaurus Headwords and Synonyms: human herpesvirus 1 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term human herpesvirus 1 名詞 一般 * * * * 単純ヘルペスウイルス1型 タンジュンヘルペスウイ...ルス1ガタ タンジュンヘルペスーイルスイチガタ Thesaurus2015 200906015205132965 C LS07 UNKNOWN_2 human herpesvirus 1

  8. Simultaneous radioimmunoassay for specific antibodies to members of the human herpesvirus group

    International Nuclear Information System (INIS)

    Gehle, W.D.; Smith, K.O.; Fuccillo, D.A.; Perry, A.; Andrese, A.P.

    1979-01-01

    A method is described for the simultaneous radioimmunoassay (RIA) for antibody to members of the human herpesvirus group. The RIA is compared with some of the conventional serologic techniques used to quantitate antibody to these viruses (Epstein-Barr virus, cytomegalovirus, herpesvirus type 1 and varicella-zoster virus). Color-coded beads, each coated with the antigens of a different herpesvirus, were simultaneously placed in a well which contained a human serum to be assayed for antibody to each of these 4 viruses. The results of this test were compared with the results obtained when the serum was assayed for antibody to the 4 viruses in 4 separate tests. We conclude that the antigen-antibody reactions do not significantly interfere with each other when a serum is assayed for antibody to the 4 viruses simultaneously. A comparison of the RIA with conventional serologic techniques shows excellent correlation in the antibody titers obtained. Features of the solid-phase RIA allow significant savings of time, reagents and space, and thus make it feasible for the small laboratory to screen large numbers of sera for antibody to a variety of antigens. (Auth.)

  9. Animal herpesviruses and their zoonotic potential for cross-species infection

    Directory of Open Access Journals (Sweden)

    Grzegorz Woźniakowski

    2015-05-01

    Full Text Available Herpesviruses of humans and animals cause severe diseases that influence not only the health and epidemiological status but are also economically important in the context of food production. The members of Herpesviridae are host specific agents that also share many properties that potentially make them capable of crossing the species barriers. The objective of presented review paper was to summarize the relationship between herpesviruses of animals and humans and their zoonotic potential. In humans, the most epidemiologically important herpesviruses are represented by Human herepesvirus-1 and Human herpesvirus-2, which are commonly known as herpes simplex virus type 1 and 2, varicella-zooster virus (VZV, Epstein-Barr virus (EBV, Kaposi’s Sarcoma-associated herpesvirus (KSHV, cytomegalovirus (CMV, as well as Human herpesviruses: HHV-6A, HHV-6B, and HHV-7. However, in terms of the potential to cross the species barrier, there are a few herpesviruses, including B virus disease (CeHV-1, Marek’s disease virus (MDV, Equid herpesvirus-1 (EHV-1 or pseudorabies virus (PRV, which are potentially able to infect different hosts. To summarize, in advantageous conditions the host specific herpesviruses may pose a threat for public health but also may exert a negative impact on the economical aspects of animal production. The most probable of these are zoonotic infections caused by B virus disease; however, close contact between infected animal hosts and humans may lead to transmission and replication of other Herpesviridae members.

  10. Identification of proteins specific for human herpesvirus 6-infected human T cells

    International Nuclear Information System (INIS)

    Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

    1989-01-01

    Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpes viruses reacted with few HHV-6-infected cell proteins, and only a 135,000-M/sub r/ polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105K and gp92k, gp116k, gp64k, and gp54k, and gp102k

  11. No increased sperm DNA fragmentation index in semen containing human papillomavirus or herpesvirus

    DEFF Research Database (Denmark)

    Kaspersen, Maja Døvling; Bungum, Mona; Fedder, Jens

    2013-01-01

    It remains unknown whether human papillomaviruses (HPVs) or human herpesviruses (HHVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen from 76 sperm donors was examined by a PCR......-based hybridization array that identifies all HHVs and 35 of the most common HPVs. Sperm DNA integrity was determined by the sperm chromatin structure assay. HPVs or HHVs, or both, were found in 57% of semen samples; however, sperm DNA fragmentation index was not increased in semen containing these viruses....

  12. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP Proteins with Implications for Human Disease

    Directory of Open Access Journals (Sweden)

    Marshall V. Williams

    2016-12-01

    Full Text Available The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase, as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer.

  13. Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus.

    OpenAIRE

    Takahashi, K; Sonoda, S; Higashi, K; Kondo, T; Takahashi, H; Takahashi, M; Yamanishi, K

    1989-01-01

    Human herpesvirus 6 (HHV-6)-related virus was isolated from CD4+ CD8- and CD3+ CD4+ mature T lymphocytes but could not be isolated from CD4- CD8+, CD4- CD8-, and CD3- T cells in the peripheral blood of exanthem subitum patients. HHV-6-related virus predominantly infected CD4+ CD8+, CD4+ CD8-, and CD3+ CD4+ cells with mature phenotypes and rarely infected CD4- CD8+ cells from cord blood mononuclear cells, which suggested predominant CD4 mature T-lymphocyte tropism of HHV-6-related virus.

  14. Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods

    OpenAIRE

    Speicher, David J; Johnson, Newell W

    2012-01-01

    Abstract Background Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 vi...

  15. High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa

    NARCIS (Netherlands)

    W. Schaftenaar (Willem); G.M.G.M. Verjans (George); S. Getu (Sarah); J.A. McIntyre (James); H.E. Struthers (Helen); A.D.M.E. Osterhaus (Albert); R.P.H. Peters (Remco)

    2014-01-01

    textabstractSeroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of

  16. Lack of association between human herpesvirus and vestibular schwannoma: analysis of 121 cases.

    Science.gov (United States)

    Bhimrao, Sanjiv K; Maguire, John; Garnis, Cathie; Tang, Patrick; Lea, Jane; Akagami, Ryojo; Westerberg, Brian D

    2015-03-01

    To assess for the presence of human herpesvirus (HHV) using immunohistochemical and polymerase chain reaction (PCR) assay in surgically excised vestibular schwannoma (VS) samples. Cross-sectional study. A retrospective laboratory-based study of tumors from patients with vestibular schwannoma. Tissue microarrays (TMAs) representing sporadic and NF2-associated VS from 121 patients, as well as appropriate positive and negative controls, were studied. TMA sections were immunostained using antibodies directed against HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, and HHV-8. PCR was used for the detection of all 8 known human herpesviruses. There was no detectable HHV (HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, HHV-8) by immunohistochemistry in any of the 121 cases of sporadic and NF2 cases analyzed. These data were further validated by DNA sequence analyses using PCR in a subset of the VS samples, all of which were found to be negative for all HHV. The data offer no support for an association between HHV and the development of sporadic or NF2-associated VS in humans. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  17. Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants.

    Science.gov (United States)

    Gantt, Soren; Orem, Jackson; Krantz, Elizabeth M; Morrow, Rhoda Ashley; Selke, Stacy; Huang, Meei-Li; Schiffer, Joshua T; Jerome, Keith R; Nakaganda, Annet; Wald, Anna; Casper, Corey; Corey, Lawrence

    2016-07-01

    Human herpesvirus (HHV) infections are common during infancy. Primary infections are frequently asymptomatic and best studied prospectively by using direct viral detection. Oropharyngeal swab specimens were collected weekly from Ugandan newborn infants, their mothers, and other children in the household. Blood specimens were collected every 4 months. Samples were tested for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6A, HHV-6B, and HHV-8, using quantitative polymerase chain reaction. Thirty-two infants, 32 mothers, and 49 other household children were followed for a median of 57 weeks. Seventeen mothers had human immunodeficiency virus type 1 (HIV) infection; no infants acquired HIV-1. The 12-month incidence of postnatal infection was 76% for HHV-6B, 59% for CMV, 47% for EBV, 8% for HSV-1, and 0% for HHV-8. The quantity of oropharyngeal shedding by contacts was associated with HHV-6A or HHV-6B transmission. Maternal HIV-1 infection was associated with EBV transmission, while breastfeeding and younger child contacts were associated with CMV transmission. Except for HSV-1, primary HHV infections were subclinical. By capturing exposures and acquisition events, we found that the incidence and risk factors of infection vary by HHV type. HSV-1 infection, unlike other HHV infections, caused acute clinical illness in these infants. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

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    Elena Sandalova

    Full Text Available Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR, proliferation (Ki-67/Bcl-2(low and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV. CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

  19. Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Holst, Peter Johannes

    2000-01-01

    Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice...

  20. Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

    NARCIS (Netherlands)

    van Zeijl, J.H.; Bakkers, J.; Wilbrink, B.; Melchers, W.J.; Mullaart, R.A.; Galama, J.M.

    2005-01-01

    During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza

  1. Epstein-Barr virus and human herpesvirus type 8 infections of the central nervous system.

    Science.gov (United States)

    Volpi, Antonio

    2004-06-01

    In developing guidelines for the improved management of herpesvirus infections of the central nervous system (CNS), the International Herpes Management Forum (IHMF) has studied Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8)- related diseases. EBV has been associated with numerous CNS diseases including meningitis, encephalitis and post transplant lymphoproliferative disorder (PTLD). The pathogenesis of EBV-associated CNS disorders is not completely understood but may be due to direct virus invasion of the CNS. Alternatively, damage may be immunologically mediated by infiltration of cytotoxic CD8+ lymphocytes into neural tissue or deposition of antibody-antigen complexes. The IHMF recommends that diagnosis of EBV infections of the CNS may involve polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) for EBV DNA but the sensitivity and specificity of the technique remains to be determined. Furthermore, the value of PCR in this context may be limited as EBV DNA is often detected in patients without neurological symptoms. Antiviral therapy has not demonstrated clinical efficacy in the treatment of EBV-related CNS disorders. CNS complications of HHV-8 infection are rare, but the virus has been associated with AIDS-dementia complex, amyotrophic lateral sclerosis (ALS) and primary CNS lymphoma; however these links remain to be proven.

  2. LCN6, a novel human epididymal lipocalin

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    Soundararajan Rama

    2003-11-01

    Full Text Available Abstract Background The lipocalin (LCN family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. Methods and Results LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. Conclusions LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility.

  3. Human herpesvirus-8 positive iatrogenic Kaposi's sarcoma in the setting of refractory ulcerative colitis.

    Science.gov (United States)

    Duh, Erica; Fine, Sean

    2017-12-16

    Although Kaposi sarcoma (KS) has been more traditionally considered an AIDS-defining illness, it may also be seen in individuals on immunosuppresive therapy. We report a case of a patient who presented to the hospital in the setting of increasingly refractory ulcerative colitis. Computed tomography scan of the abdomen was consistent with sigmoid diverticulititis and blood cultures were positive for Klebsiella. After a course of antibiotics with resolution of infection, a colonoscopy was performed to evaluate his diverticulitis and incidentally revealed a new rectal tumor. Immunohistochemistry showed the tumor was consistent with KS, with cells staining strongly positive for human herpesvirus-8. This case not only illustrates a rare case of KS found in an HIV-negative individual, but it also highlights the importance of considering an alternative diagnosis in a patient refractory to medical treatment. We discuss the management and care of an ulcerative colitis patient diagnosed with KS on immunosuppressive therapy.

  4. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

    Science.gov (United States)

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

    2018-01-01

    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

  5. Reactivation of chromosomally integrated human herpesvirus-6 by telomeric circle formation.

    Directory of Open Access Journals (Sweden)

    Bhupesh K Prusty

    Full Text Available More than 95% of the human population is infected with human herpesvirus-6 (HHV-6 during early childhood and maintains latent HHV-6 genomes either in an extra-chromosomal form or as a chromosomally integrated HHV-6 (ciHHV-6. In addition, approximately 1% of humans are born with an inheritable form of ciHHV-6 integrated into the telomeres of chromosomes. Immunosuppression and stress conditions can reactivate latent HHV-6 replication, which is associated with clinical complications and even death. We have previously shown that Chlamydia trachomatis infection reactivates ciHHV-6 and induces the formation of extra-chromosomal viral DNA in ciHHV-6 cells. Here, we propose a model and provide experimental evidence for the mechanism of ciHHV-6 reactivation. Infection with Chlamydia induced a transient shortening of telomeric ends, which subsequently led to increased telomeric circle (t-circle formation and incomplete reconstitution of circular viral genomes containing single viral direct repeat (DR. Correspondingly, short t-circles containing parts of the HHV-6 DR were detected in cells from individuals with genetically inherited ciHHV-6. Furthermore, telomere shortening induced in the absence of Chlamydia infection also caused circularization of ciHHV-6, supporting a t-circle based mechanism for ciHHV-6 reactivation.

  6. Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6

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    Derek J. Hanson

    2018-06-01

    Full Text Available Human herpesvirus (HHV 6 is thought to remain clinically latent in most individuals after primary infection and to reactivate to cause disease in persons with severe immunosuppression. In allogeneic hematopoietic stem cell transplant recipients, reactivation of HHV-6 species B is a considerable cause of morbidity and mortality. HHV-6B reactivation is the most frequent cause of infectious meningoencephalitis in this setting and has been associated with a variety of other complications such as graft rejection and acute graft versus host disease. This has inspired efforts to develop HHV-6-targeted immunotherapies. Basic knowledge of HHV-6-specific adaptive immunity is crucial for these endeavors, but remains incomplete. Many studies have focused on specific HHV-6 antigens extrapolated from research on human cytomegalovirus, a genetically related betaherpesvirus. Challenges to the study of HHV-6-specific T-cell immunity include the very low frequency of HHV-6-specific memory T cells in chronically infected humans, the large genome size of HHV-6, and the lack of an animal model. This review will focus on emerging techniques and methodological improvements that are beginning to overcome these barriers. Population-prevalent antigens are now becoming clear for the CD4+ T-cell response, while definition and ranking of CD8+ T-cell antigens and epitopes is at an earlier stage. This review will discuss current knowledge of the T-cell response to HHV-6, new research approaches, and translation to clinical practice.

  7. Association between human herpesvirus infections and dementia or mild cognitive impairment: a systematic review protocol.

    Science.gov (United States)

    Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith; Hayward, Andrew C; Mavrodaris, Angelique; Ridha, Basil H; Rossor, Martin; Thomas, Sara L; Smeeth, Liam

    2017-06-23

    Persisting neurotropic viruses are proposed to increase the risk of dementia, but evidence of association from robust, adequately powered population studies is lacking. This is essential to inform clinical trials of targeted preventive interventions. We will carry out a comprehensive systematic review of published and grey literature of the association between infection with, reactivation of, vaccination against or treatment of any of the eight human herpesviruses and dementia or mild cognitive impairment. We will search the Cochrane Library, Embase, Global Health, Medline, PsycINFO, Scopus, Web of Science, clinical trials registers, the New York Academy of Medicine Grey Literature Report, Electronic Theses Online Service through the British Library and the ISI Conference Proceedings Citation Index for randomised controlled trials, cohort, caseâ€"control, case crossover or self-controlled case series studies reported in any language up to January 2017. Titles, abstracts and full-text screening will be conducted by two researchers independently. Data will be extracted systematically from eligible studies using a piloted template. We will assess risk of bias of individual studies in line with the Cochrane Collaboration tool. We will conduct a narrative synthesis, grouping studies by exposure and outcome definitions, and will describe any differences by population subgroups and dementia subtypes. We will consider performing meta-analyses if there are adequate numbers of sufficiently homogeneous studies. The overall quality of cumulative evidence will be assessed using selected Grading of Recommendations, Assessment, Development and Evaluations criteria. As this is a review of existing studies, no ethical approval is required. Results will be disseminated through a peer-reviewed publication and at national and international conferences. We anticipate the review will clarify the current extent and quality of evidence for a link between herpesviruses and dementia

  8. Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: A case control study

    Directory of Open Access Journals (Sweden)

    Ruff P

    2006-09-01

    Full Text Available Abstract Background Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. Methods We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity(n = 88, the cervix(n = 53, the prostate(n = 66, Hodgkin lymphoma(n = 83, non-Hodgkin lymphoma(n = 80, multiple myeloma(n = 94 or leukaemia(n = 203. For comparison, patients with other cancers(n = 95 or cardiovascular disease(n = 101 were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. Results There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0

  9. Development and validation of a Q-PCR based TCID50 method for human herpesvirus 6

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    Gustafsson Rasmus K L

    2012-12-01

    Full Text Available Abstract Background For titer assessment of human herpesvirus 6 (HHV-6, IFA targeting viral proteins or a TCID50 method with ocular inspection for CPE can be used. These methods rely on the subjective decision of the assessor, obstructing the ability to obtain unanimous results. Findings We have developed and validated an alternative TCID50 read-out approach where infection in the titration culture plate is assessed by viral DNA load change by quantitative PCR. A ten time increase in viral DNA load was determined as cut point for infection since that yielded a maximum correlation with viral protein expression (93%. The average intra-assay CV was 9% for quantitative PCR read-out of TCID50 compared to 45% for ocular inspection read-out of TCID50, 14% for IFA read-out of TCID50, and 43% for an infectious units approach using IFA. The average inter-assay CV for quantitative PCR read-out of TCID50 was 73%, compared to 66%, 25% and 77% for the ocular inspection read-out for TCID50, IFA read-out of TCID50 and infectious unit approaches respectively. Conclusions The quantitative PCR based read-out of TCID50 proved to be more robust and easier to interpret than traditional TCID50 assessment approaches for HHV-6, and therefore it might be considered as an alternative method.

  10. Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

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    Naoyuki Tanuma

    2014-01-01

    Full Text Available To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6 infection, we measured the levels of oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG and hexanoyl-lysine adduct (HEL, tau protein, and cytokines in cerebrospinal fluid (CSF obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy (n=16 and complex febrile seizures associated with HHV-6 (HHV-6 complex FS (n=10. We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure, the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.

  11. The genome of herpesvirus saimiri C488 which is capable of transforming human T cells

    International Nuclear Information System (INIS)

    Ensser, Armin; Thurau, Mathias; Wittmann, Sabine; Fickenscher, Helmut

    2003-01-01

    Herpesvirus saimiri (HVS), the rhadinovirus prototype, is apathogenic in the persistently infected natural host, the squirrel monkey, but causes acute T cell leukemia in other New World primate species. In contrast to subgroups A and B, only strains of HVS subgroup C such as C488 are capable of transforming primary human T cells to stable antigen-independent growth in culture. Here, we report the complete 155-kb genome sequence of the transformation-competent HVS strain C488. The A+T-rich unique L-DNA of 113,027 bp encodes at least 77 open reading frames and 5 URNAs. In addition to the viral oncogenes stp and tip, only a few genes including the transactivator orf50 and the glycoprotein orf51 are highly divergent. In a series of new primary HVS isolates, the subgroup-specific divergence of the orf50/orf51 alleles was studied. In these new isolates, the orf50/orf51 alleles of the respective subgroup segregate with the stp and/or tip oncogene alleles, which are essential for transformation

  12. Estimating immunoregulatory gene networks in human herpesvirus type 6-infected T cells

    International Nuclear Information System (INIS)

    Takaku, Tomoiku; Ohyashiki, Junko H.; Zhang, Yu; Ohyashiki, Kazuma

    2005-01-01

    The immune response to viral infection involves complex network of dynamic gene and protein interactions. We present here the dynamic gene network of the host immune response during human herpesvirus type 6 (HHV-6) infection in an adult T-cell leukemia cell line. Using a pathway-focused oligonucleotide DNA microarray, we found a possible association between chemokine genes regulating Th1/Th2 balance and genes regulating T-cell proliferation during HHV-6B infection. Gene network analysis using an integrated comprehensive workbench, VoyaGene, revealed that a gene encoding a TEC-family kinase, ITK, might be a putative modulator in the host immune response against HHV-6B infection. We conclude that Th2-dominated inflammatory reaction in host cells may play an important role in HHV-6B-infected T cells, thereby suggesting the possibility that ITK might be a therapeutic target in diseases related to dysregulation of Th1/Th2 balance. This study describes a novel approach to find genes related with the complex host-virus interaction using microarray data employing the Bayesian statistical framework

  13. Feline herpesvirus.

    Science.gov (United States)

    Gaskell, Rosalind; Dawson, Susan; Radford, Alan; Thiry, Etienne

    2007-01-01

    Feline herpesvirus (FHV-1; felid herpesvirus 1 (FeHV-1)) is an alphaherpesvirus of cats closely related to canine herpesvirus-1 and phocine herpesvirus-1. There is only one serotype of the virus and it is relatively homogenous genetically. FeHV-1 is an important cause of acute upper respiratory tract and ocular disease in cats. In addition, its role in more chronic ocular disease and skin lesions is increasingly being recognised. Epidemiologically, FeHV-1 behaves as a typical alphaherpesvirus whereby clinically recovered cats become latently infected carriers which undergo periodic episodes of virus reactivation, particularly after a stress. The primary site of latency is the trigeminal ganglion. Conventional inactivated and modified-live vaccines are available and protect reasonably well against disease but not infection, although viral shedding may be reduced. Genetically engineered vaccines have also been developed, both for FeHV-1 and as vector vaccines for other pathogens, but none is as yet marketed.

  14. Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

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    Negin N Blattman

    2014-04-01

    Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

  15. Serological evidence of herpesvirus infection in gibbons

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    Ratanakorn Parntep

    2002-05-01

    Full Text Available Abstract Background Herpesviruses are not only infectious agents of worldwide distribution in humans, but have also been demonstrated in various non-human primates as well. Seventy-eight gibbons were subjected to serological tests by ELISA for herpes simplex virus type 1 (HSV-1, herpes simplex virus type 2 (HSV-2, Epstein-Barr virus (EBV and cytomegalovirus (CMV. Results The prevalence of IgG antibodies against HSV-1, HSV-2, EBV and CMV was 28.2%, 28.2%, 14.1% and 17.9%, respectively. Conclusions Antigenic cross-reactivity is expected to exist between the human herpesviruses and gibbon herpesviruses. Gibbons have antibodies to human herpesviruses that may reflect zoonotic infection with human herpesviruses or infection with indigenous gibbon herpesviruses. Therefore, it is difficult to draw concrete conclusions from serological studies alone. Identification should be based on further isolation and molecular characterization of viruses from seropositive animals.

  16. Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

    Science.gov (United States)

    Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie

    2013-12-01

    Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Diagnostic assays for active infection with human herpesvirus 6 (HHV-6).

    Science.gov (United States)

    Caserta, Mary T; Hall, Caroline Breese; Schnabel, Kenneth; Lofthus, Geraldine; Marino, Andrea; Shelley, Lynne; Yoo, Christina; Carnahan, Jennifer; Anderson, Linda; Wang, Hongyue

    2010-05-01

    Human herpesvirus 6 (HHV-6) causes ubiquitous infection in early childhood with lifelong latency or persistence. Reactivation of HHV-6 has been associated with multiple diseases including encephalitis. Chromosomal integration of HHV-6 also occurs. Previous studies have suggested that the detection of HHV-6 DNA in plasma is an accurate marker of active viral replication. We sought to determine whether PCR assays on plasma could correctly differentiate between primary HHV-6 infection, chromosomal integration of HHV-6 and latent HHV-6 infection. We performed qualitative PCR, real-time quantitative PCR (RQ-PCR), and reverse-transcriptase PCR (RT-PCR) assays on samples of peripheral and cord blood mononuclear cells, as well as plasma, from groups of subjects with well defined HHV-6 infection, including subjects with chromosomally integrated HHV-6. The detection of HHV-6 DNA in plasma was 92% sensitive compared to viral isolation for the identification of primary infection with HHV-6. All plasma samples from infants with chromosomally integrated HHV-6 had HHV-6 DNA detectable in plasma while only 5.6% were positive by RT-PCR. The specificity of plasma PCR for active replication of HHV-6 was 84% compared to viral culture while the specificity of RT-PCR was 98%. Our results demonstrate that qualitative or quantitative PCR of plasma is insufficient to distinguish between active viral replication and chromosomal integration with HHV-6. We found a higher specificity of RT-PCR performed on PBMC samples compared to PCR or RQ-PCR performed on plasma when evaluating samples for active HHV-6 replication. Copyright 2010 Elsevier B.V. All rights reserved.

  18. Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

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    Özlem Su

    2008-12-01

    Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

  19. Seroprevalence of Human herpesvirus 8 (HHV-8 and incidence of Kaposi's sarcoma in Iran

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    Nategh Rakhshandeh

    2011-04-01

    Full Text Available Abstract Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8 infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%, renal transplant recipients (25% and HIV (45.7% patients compared to blood donors (2%. Kaposi's sarcoma (KS is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

  20. Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

    Science.gov (United States)

    Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

    2013-11-01

    Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (Preactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

  1. High Level Human Herpesvirus-6 Viremia Associated with onset of Stevens-Johnson Syndrome: Report of 2 Cases

    Science.gov (United States)

    Peppercorn, Amanda F.; Miller, Melissa B.; Fitzgerald, David; Weber, David J.; Groben, Pamela A.; Cairns, Bruce A.

    2015-01-01

    The pathogenesis of Stevens Johnson Syndrome (SJS) remains obscure but it has been associated with various infectious agents, including members of the Herpes virus family. We present the first report of high level human herpesvirus-6 (HHV-6) viremia at the onset of SJS suggesting a possible new association. This finding supports the need for further investigation into the possible relationship between HHV-6 and SJS which may illuminate the pathogenesis of SJS and bring us closer to achieving enhanced prevention and treatment of this rare disease. PMID:20182379

  2. Herpesvirus systematics☆

    Science.gov (United States)

    Davison, Andrew J.

    2010-01-01

    This paper is about the taxonomy and genomics of herpesviruses. Each theme is presented as a digest of current information flanked by commentaries on past activities and future directions. The International Committee on Taxonomy of Viruses recently instituted a major update of herpesvirus classification. The former family Herpesviridae was elevated to a new order, the Herpesvirales, which now accommodates 3 families, 3 subfamilies, 17 genera and 90 species. Future developments will include revisiting the herpesvirus species definition and the criteria used for taxonomic assignment, particularly in regard to the possibilities of classifying the large number of herpesviruses detected only as DNA sequences by polymerase chain reaction. Nucleotide sequence accessions in primary databases, such as GenBank, consist of the sequences plus annotations of the genetic features. The quality of these accessions is important because they provide a knowledge base that is used widely by the research community. However, updating the accessions to take account of improved knowledge is essentially reserved to the original depositors, and this activity is rarely undertaken. Thus, the primary databases are likely to become antiquated. In contrast, secondary databases are open to curation by experts other than the original depositors, thus increasing the likelihood that they will remain up to date. One of the most promising secondary databases is RefSeq, which aims to furnish the best available annotations for complete genome sequences. Progress in regard to improving the RefSeq herpesvirus accessions is discussed, and insights into particular aspects of herpesvirus genomics arising from this work are reported. PMID:20346601

  3. Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

    DEFF Research Database (Denmark)

    Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

    2008-01-01

    Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...

  4. Proteflazid® and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections.

    Science.gov (United States)

    Kaminsky, Vjacheslav; Chernyshov, Viktor; Grynevych, Oleksandr; Benyuk, Vasil; Kornatskaya, Alla; Shalko, Miroslava; Usevich, Igor; Revenko, Oleg; Shepetko, Maxim; Solomakha, Ludmila

    2017-03-21

    Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).

  5. Structural Proteomics of Herpesviruses

    Science.gov (United States)

    Leroy, Baptiste; Gillet, Laurent; Vanderplasschen, Alain; Wattiez, Ruddy

    2016-01-01

    Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections. PMID:26907323

  6. Prevalence and correlates of human herpesvirus 8 infection among Peruvian men who have sex with men.

    Science.gov (United States)

    Guanira, Juan V; Casper, Corey; Lama, Javier R; Morrow, Rhoda; Montano, Silvia M; Caballero, Patricia; Suárez, Luis; Whittington, William L H; Wald, Anna; Sanchez, Jorge; Celum, Connie

    2008-12-15

    Infection with human herpesvirus 8 (HHV-8) is common among men who have sex with men (MSM) in North America and Europe and is also found to be endemic in some regions of South America. Little is known about HHV-8 prevalence and its correlates among MSM in the Andean region. We assessed HHV-8 seroprevalence among 497 MSM recruited for the 2002 Peruvian HIV sentinel surveillance program using a combined HHV-8 enzyme immunoassay and immunofluorescence assay algorithm. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) to determine the association between selected covariates and HHV-8 seropositivity. One hundred thirty-one (66.5%, 95% CI 63.1% to 69.9%) of 197 HIV-infected and 80 (26.7%, 95% CI 24.4% to 29.0%) of 300 HIV-uninfected MSM had serologic evidence of HHV-8 infection. Factors independently associated with HHV-8 infection were education<12 years (OR 1.7, 95% CI 1.1 to 2.7), anal receptive sex with the last partner (OR 2.0, 95% CI 1.2 to 3.3), self-reported sexually transmitted infection symptoms during the last year (OR 1.9, 95% CI 1.2 to 3.0), coinfection with HIV (OR 4.2, 95% CI 2.8 to 6.4) and chronic hepatitis B (OR 4.9, 95% CI 1.5 to 15.8). MSM with long-standing HIV infection were more likely to have serologic evidence of HHV-8 infection when compared with men with recently acquired HIV (OR 3.8, 95% CI 1.7 to 9.1). HHV-8 infection is common among both HIV-infected and HIV-negative MSM in Lima, Peru. HHV-8 seropositivity is correlated with anal receptive sex, self-reported sexually transmitted infection symptoms, and HIV infection among these MSM and thus seems to be sexually transmitted. HHV-8 infection seems to be acquired after HIV infection, suggesting that future studies should evaluate the mode of HHV-8 transmission and prevention strategies among HIV-uninfected MSM.

  7. Human herpesvirus-8 infection leads to expansion of the preimmune/natural effector B cell compartment.

    Directory of Open Access Journals (Sweden)

    Silvia Della Bella

    Full Text Available BACKGROUND: Human herpesvirus-8 (HHV-8 is the etiological agent of Kaposi's sarcoma (KS and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS. METHODOLOGY/PRINCIPAL FINDINGS: Circulating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS (n = 47; 2- subjects HHV-8 positive and cKS negative (HSP (n = 10; 3- healthy controls, HHV-8 negative and cKS negative (HC (n = 43. The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load. CONCLUSIONS/SIGNIFICANCE: Our results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.

  8. Prevalence and Correlates of Human Herpesvirus 8 Infection among Peruvian Men who have Sex with Men

    Science.gov (United States)

    Guanira, Juan V.; Casper, Corey; Lama, Javier R.; Morrow, Rhoda; Montano, Silvia M; Caballero, Patricia; Suárez, Luis; Whittington, William L. H.; Wald, Anna; Sanchez, Jorge; Celum, Connie

    2011-01-01

    Background Infection with human herpesvirus 8 (HHV-8) is common among men who have sex with men (MSM) in North America and Europe, and is also found to be endemic in some regions of South America. Little is known about HHV-8 prevalence and its correlates among MSM in the Andean region. Methods We assessed HHV-8 seroprevalence among 497 MSM recruited for the 2002 Peruvian HIV sentinel surveillance program using a combined HHV-8 enzyme immunoassay and immunofluorescence assay algoritm. Logistic regression was used to estimate Odds Ratios (OR) and their 95% confidence intervals (CI) to determine the association between selected covariates and HHV-8 seropositivity. Results 483 (97%) of 497 men had stored sera and demographic data available for analysis. 131 (66.5%, 95% CI 63.1%-69.9%) of 197 HIV-infected and 80 (26.7%, 95% CI 24.4%-29.0%) of 300 HIV-uninfected MSM had serologic evidence of HHV-8 infection. Factors independently associated with HHV-8 infection were education <12 years (OR 1.7, 95% CI 1.1-2.7), anal receptive sex with the last partner (OR 2.0, 95% CI 1.2-3.3), self-reported STI symptoms during the last year (OR: 1.9, 95% CI 1.2-3.0), and co-infection with HIV (OR 4.2, 95% CI 2.8-6.4) and Chronic Hepatitis B (OR 4.9, 95% CI 1.5-15.8). MSM with long-standing HIV infection were more likely to have serologic evidence of HHV-8 infection when compared to men with recently-acquired HIV (OR: 3.8, 95% CI 1.7-9.1). Conclusions HHV-8 infection is common among both HIV-infected and negative MSM in Lima, Peru. HHV-8 seropositivity is correlated with anal receptive sex, self-reported STI symptoms, and HIV infection among these MSM, and thus appears to be sexually transmitted. HHV-8 infection appears to be acquired after HIV infection, suggesting that future studies should evaluate the mode of HHV-8 transmission and prevention strategies among HIV-infected MSM. PMID:18989224

  9. Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods.

    Science.gov (United States)

    Speicher, David J; Johnson, Newell W

    2012-09-11

    Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months. HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available in many parts of the world, including those with high prevalence of KS and HHV-8. A new molecular facility with stringent three-phase workflow was established, adhering to NPAAC and CLSI guidelines. Three fully validated quantitative assays were developed: two for detection and quantification of HHV-8; one for GAPDH, necessary for normalisation of viral loads in tissue and peripheral blood. The HHV-8 ORF73 and ORF26 qPCR assays were 100% specific. All qPCR assays, displayed a broad dynamic range (102 to 1010 copies/μL TE Buffer) with a limit of detection of 4.85x103, 5.61x102, and 2.59x102 copies/μL TE Buffer and a limit of quantification of 4.85x103, 3.01x102, and 1.38x102 copies/μL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and GAPDH respectively.The assays were tested on a panel of 35 KS biopsies from Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV-8 copies/μL DNA extract (range: 4.37x103 to 1.47x106 copies/μL DNA extract): When normalised these equate to an average viral load of 2.44x104 HHV-8 copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells). These are the first fully optimised, validated and MIQE compliant HHV-8 qPCR assays established in Australia. They worked well for qualitative detection of HHV-8 in archival tissue, and are well-suited for quantitative detection in whole blood. They are now

  10. Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods

    Directory of Open Access Journals (Sweden)

    Speicher David J

    2012-09-01

    Full Text Available Abstract Background Human herpesvirus 8 (HHV-8, the aetiological agent of Kaposi’s sarcoma (KS, multicentric Castleman’s disease (MCD, and primary effusion lymphoma (PEL is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months. HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available in many parts of the world, including those with high prevalence of KS and HHV-8. Methods A new molecular facility with stringent three-phase workflow was established, adhering to NPAAC and CLSI guidelines. Three fully validated quantitative assays were developed: two for detection and quantification of HHV-8; one for GAPDH, necessary for normalisation of viral loads in tissue and peripheral blood. Results The HHV-8 ORF73 and ORF26 qPCR assays were 100% specific. All qPCR assays, displayed a broad dynamic range (102 to 1010 copies/μL TE Buffer with a limit of detection of 4.85x103, 5.61x102, and 2.59x102 copies/μL TE Buffer and a limit of quantification of 4.85x103, 3.01x102, and 1.38x102 copies/μL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and GAPDH respectively. The assays were tested on a panel of 35 KS biopsies from Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV-8 copies/μL DNA extract (range: 4.37x103 to 1.47x106 copies/μL DNA extract: When normalised these equate to an average viral load of 2.44x104 HHV-8 copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells. Conclusions These are the first fully optimised, validated and MIQE compliant HHV-8 qPCR assays established in Australia. They worked well for qualitative detection of HHV-8 in archival tissue, and are well

  11. Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway

    DEFF Research Database (Denmark)

    Øster, Bodil; Bundgaard, B; Hupp, T R

    2008-01-01

    Here, we demonstrate that human herpesvirus 6B (HHV-6B) infection upregulates the tumour suppressor p53 and induces phosphorylation of p53 at Ser392. Interestingly, phosphorylation at the equivalent site has previously been shown to correlate with p53 tumour suppression in murine models. Although...

  12. An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Vaibhav [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Darmani, Nissar A.; Thrush, Gerald R. [Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Shukla, Deepak, E-mail: dshukla@uic.edu [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2009-12-18

    Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

  13. The genome of herpesvirus papio 2 is closely related to the genomes of human herpes simplex viruses.

    Science.gov (United States)

    Bigger, John E; Martin, David W

    2003-06-01

    Infection of baboons (Papio species) with herpesvirus papio 2 (HVP-2) produces a disease that is clinically similar to herpes simplex virus (HSV-1 and HSV-2) infection of humans. The development of a primate model of simplexvirus infection based on HVP-2 would provide a powerful resource to study virus biology and test vaccine strategies. In order to characterize the molecular biology of HVP-2 and justify further development of this model system we have constructed a physical map of the HVP-2 genome. The results of these studies have identified the presence of 26 reading frames that closely resemble HSV homologues. Furthermore, the HVP-2 genome shares a collinear arrangement with the genome of HSV. These studies further validate the development of the HVP-2 model as a surrogate system to study the biology of HSV infections.

  14. An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

    International Nuclear Information System (INIS)

    Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

    2009-01-01

    Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

  15. Multiple sclerosis and herpesvirus interaction

    Directory of Open Access Journals (Sweden)

    Guilherme Sciascia do Olival

    2013-09-01

    Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

  16. Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8

    DEFF Research Database (Denmark)

    Hansen, P B; Penkowa, M; Kirk, O

    2000-01-01

    The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8...

  17. Kaposi sarcoma herpesvirus pathogenesis

    Science.gov (United States)

    Koch, Sandra; Schulz, Thomas F.

    2017-01-01

    Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

  18. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Christensen, Tove; Hansen, Hans Jacob

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...

  19. The first genome sequence of a metatherian herpesvirus: Macropodid herpesvirus 1.

    Science.gov (United States)

    Vaz, Paola K; Mahony, Timothy J; Hartley, Carol A; Fowler, Elizabeth V; Ficorilli, Nino; Lee, Sang W; Gilkerson, James R; Browning, Glenn F; Devlin, Joanne M

    2016-01-22

    While many placental herpesvirus genomes have been fully sequenced, the complete genome of a marsupial herpesvirus has not been described. Here we present the first genome sequence of a metatherian herpesvirus, Macropodid herpesvirus 1 (MaHV-1). The MaHV-1 viral genome was sequenced using an Illumina MiSeq sequencer, de novo assembly was performed and the genome was annotated. The MaHV-1 genome was 140 kbp in length and clustered phylogenetically with the primate simplexviruses, sharing 67% nucleotide sequence identity with Human herpesviruses 1 and 2. The MaHV-1 genome contained 66 predicted open reading frames (ORFs) homologous to those in other herpesvirus genomes, but lacked homologues of UL3, UL4, UL56 and glycoprotein J. This is the first alphaherpesvirus genome that has been found to lack the UL3 and UL4 homologues. We identified six novel ORFs and confirmed their transcription by RT-PCR. This is the first genome sequence of a herpesvirus that infects metatherians, a taxonomically unique mammalian clade. Members of the Simplexvirus genus are remarkably conserved, so the absence of ORFs otherwise retained in eutherian and avian alphaherpesviruses contributes to our understanding of the Alphaherpesvirinae. Further study of metatherian herpesvirus genetics and pathogenesis provides a unique approach to understanding herpesvirus-mammalian interactions.

  20. Virus and host-specific differences in oral human herpesvirus shedding kinetics among Ugandan women and children.

    Science.gov (United States)

    Matrajt, Laura; Gantt, Soren; Mayer, Bryan T; Krantz, Elizabeth M; Orem, Jackson; Wald, Anna; Corey, Lawrence; Schiffer, Joshua T; Casper, Corey

    2017-10-12

    Human herpesviruses (HHV) establish lifelong latent infection and are transmitted primarily via shedding at mucosal surfaces. Each HHV causes a unique spectrum of disease depending on the infected individual's age and immunity. We collected weekly oral swabs from young children and mothers in 32 Ugandan households for a median of one year. We characterized kinetics of oral shedding during primary and chronic infection for each virus. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and HHV-6 were shed at high rates following primary infection. The rate of oral herpes simplex virus (HSV) shedding was lower overall, and children and mothers with chronic HSV infection had lower shedding rates than children with primary infection. CMV shedding rate and viral load were higher in children with primary infection compared to children with chronic infection, and even lower in mothers with chronic infection. HHV-6 shedding rate and viral load were similar between children with primary or chronic infection, but lower in mothers. EBV shedding rate and quantity decreased less dramatically in mothers versus children, with HIV-positive mothers shedding at a higher rate than HIV-negative mothers. Each HHV has a distinct pattern of oral shedding which depends partially on the age and immune status of the host.

  1. Seroprevalence and determinants of Kaposi sarcoma-associated human herpesvirus 8 in Indian HIV-infected males.

    Science.gov (United States)

    Munawwar, Arshi; Sharma, Surendra K; Gupta, Somesh; Singh, Sarman

    2014-12-01

    In India Kaposi's sarcoma is rarely seen in AIDS patients. Hence the current belief is that the incidence of human herpesvirus-8 (HHV-8) is very low in this subcontinent, most probably due to the heterosexual route of HIV transmission. However, there is a scarcity of data on the prevalence of HHV-8 in India. In India the primary mode of HIV transmission is the heterosexual route. Therefore we aimed to determine the prevalence of antibodies against HHV-8 in North Indian HIV-infected men naive of antiretroviral therapy (ART). In a prospective study, 165 Indian adult males were recruited from an ART clinic. Blood samples were collected before administering any antiretroviral drug. The sera were tested for antibodies against HHV-8 using a commercial enzyme-linked immunosorbent assay (ELISA) kit, which detects IgG antibodies to lytic antigens of HHV-8. All positive samples were confirmed for the presence of anti-HHV-8 antibodies using an indirect immunofluorescence assay (IFA). The IFA kit is intended to detect primary, latent, persistent, or reactivated infection of HHV-8. Of the 165 males, 43 (26.06%) were positive by ELISA while 26 (15.8%) were also positive by IFA. Seroprevalence decreased with increasing age (p<0.05). Factors independently associated with HHV-8 infection were younger age group and alcohol consumption. These findings suggest that even in a heterosexual population, HHV-8 can be transmitted frequently.

  2. Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    International Nuclear Information System (INIS)

    Kokuina, Elena; Dominguez Alvarez, Carlos; Noa Pedroso, Guillermo; Martinez Rodriguez Pedro Ariel

    2009-01-01

    The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19 +) and NK cells (CD3 -C D56 +) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20 +) and T cells (CD3 +) , similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

  3. Role of dendritic cells infected with human herpesvirus 6 in virus transmission to CD4+ T cells

    International Nuclear Information System (INIS)

    Takemoto, Masaya; Imasawa, Takayoshi; Yamanishi, Koichi; Mori, Yasuko

    2009-01-01

    Human herpesvirus 6 (HHV-6) is a ubiquitous betaherpesvirus that predominantly infects and replicates in CD4 + T lymphocytes. However, the mechanism of HHV-6 transmission to T cells from the peripheral mucosa is unknown. Here we found that dendritic cells (DCs) can transmit HHV-6 to T cells, resulting in productive infection. In immature monocyte-derived DCs (MDDCs) infected with HHV-6, viral early and late antigens were expressed, and nucleocapsids containing a DNA core were observed, although few virions were detected in the cytoplasm by electron microscopy, indicating that the maturation of HHV-6 virions may be incomplete in MDDCs. However, HHV-6 transmission from MDDCs to stimulated CD4 + T cells occurred efficiently in coculture of these cells, but not from MDDCs culture supernatants. This transmission was partially inhibited by treating the DCs with a viral DNA synthesis blocker, indicating that viral replication in MDDCs is required for this transmission. Furthermore, myeloid DCs and plasmacytoid DCs infected with HHV-6 could also transmit the virus to stimulated T cells. Thus, DCs may be the first cell population targeted by HHV-6 and could play an important role in the virus' transmission to T cells for their further propagation

  4. Increasing seroprevalence of human herpesvirus 8 (HHV-8) with age confirms HHV-8 endemicity in Amazon Amerindians from Brazil.

    Science.gov (United States)

    Cunha, A M G; Caterino-de-Araujo, A; Costa, S C B; Santos-Fortuna, E; Boa-Sorte, N C A; Gonçalves, M S; Costa, F F; Galvão-Castro, B

    2005-09-01

    Human herpesvirus 8 (HHV-8) seroprevalences were determined in two isolated Amazon Amerindian tribes, according to age, gender and familial aggregation. Plasma and serum samples obtained from 982 Amazon Amerindians (664 Tiriyó and 318 Waiampi) were tested for antibodies against lytic and latent HHV-8 antigens by using 'in-house' immunofluorescence assays. Overall, HHV-8 seroprevalence was 56.8 % (57.4 % in the Tiriyó tribe and 55.7 % in the Waiampi tribe). Seroprevalence was independent of gender and increased linearly with age: it was 35.0 % among children aged 2-9 years, 51.4 % in adolescents (10-19 years), 72.9 % in adults and 82.3 % in adults aged >50 years. Interestingly, 44.4 % of children under 2 years of age were HHV-8-seropositive. No significant differences in seroprevalence between tribes and age groups were detected. It is concluded that HHV-8 is hyperendemic in Brazilian Amazon Amerindians, with vertical and horizontal transmission during childhood, familial transmission and sexual contact in adulthood contributing to this high prevalence in these isolated populations.

  5. Herpesviruses that Infect Fish

    Directory of Open Access Journals (Sweden)

    Moshe Kotler

    2011-11-01

    Full Text Available Herpesviruses are host specific pathogens that are widespread among vertebrates. Genome sequence data demonstrate that most herpesviruses of fish and amphibians are grouped together (family Alloherpesviridae and are distantly related to herpesviruses of reptiles, birds and mammals (family Herpesviridae. Yet, many of the biological processes of members of the order Herpesvirales are similar. Among the conserved characteristics are the virion structure, replication process, the ability to establish long term latency and the manipulation of the host immune response. Many of the similar processes may be due to convergent evolution. This overview of identified herpesviruses of fish discusses the diseases that alloherpesviruses cause, the biology of these viruses and the host-pathogen interactions. Much of our knowledge on the biology of Alloherpesvirdae is derived from research with two species: Ictalurid herpesvirus 1 (channel catfish virus and Cyprinid herpesvirus 3 (koi herpesvirus.

  6. Herpesviruses that infect fish.

    Science.gov (United States)

    Hanson, Larry; Dishon, Arnon; Kotler, Moshe

    2011-11-01

    Herpesviruses are host specific pathogens that are widespread among vertebrates. Genome sequence data demonstrate that most herpesviruses of fish and amphibians are grouped together (family Alloherpesviridae) and are distantly related to herpesviruses of reptiles, birds and mammals (family Herpesviridae). Yet, many of the biological processes of members of the order Herpesvirales are similar. Among the conserved characteristics are the virion structure, replication process, the ability to establish long term latency and the manipulation of the host immune response. Many of the similar processes may be due to convergent evolution. This overview of identified herpesviruses of fish discusses the diseases that alloherpesviruses cause, the biology of these viruses and the host-pathogen interactions. Much of our knowledge on the biology of Alloherpesvirdae is derived from research with two species: Ictalurid herpesvirus 1 (channel catfish virus) and Cyprinid herpesvirus 3 (koi herpesvirus).

  7. Herpesviruses that Infect Fish

    Science.gov (United States)

    Hanson, Larry; Dishon, Arnon; Kotler, Moshe

    2011-01-01

    Herpesviruses are host specific pathogens that are widespread among vertebrates. Genome sequence data demonstrate that most herpesviruses of fish and amphibians are grouped together (family Alloherpesviridae) and are distantly related to herpesviruses of reptiles, birds and mammals (family Herpesviridae). Yet, many of the biological processes of members of the order Herpesvirales are similar. Among the conserved characteristics are the virion structure, replication process, the ability to establish long term latency and the manipulation of the host immune response. Many of the similar processes may be due to convergent evolution. This overview of identified herpesviruses of fish discusses the diseases that alloherpesviruses cause, the biology of these viruses and the host-pathogen interactions. Much of our knowledge on the biology of Alloherpesvirdae is derived from research with two species: Ictalurid herpesvirus 1 (channel catfish virus) and Cyprinid herpesvirus 3 (koi herpesvirus). PMID:22163339

  8. Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris.

    Science.gov (United States)

    Gravel, Annie; Dubuc, Isabelle; Morissette, Guillaume; Sedlak, Ruth H; Jerome, Keith R; Flamand, Louis

    2015-06-30

    Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6- subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6- subjects (P = 0.017; 95% CI, 1.73-6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23-7.15). Analyses of telomere lengths between iciHHV-6- without angina, iciHHV-6- with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6- subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.

  9. Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

    Science.gov (United States)

    2012-05-25

    Science 1974;186:1213-1215. 11. Wilson JD, Griffin JE, Leshin M, George FW. Role of gonadal hormones in development of the sexual phenotypes. Hum Genet... Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R. Constitutive activation of Stat3 in human prostate tumors and cell lines: direct

  10. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

    Science.gov (United States)

    Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

    2012-02-01

    Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

  11. Co-infection of human herpesvirus type 2 (HHV-2) and human immunodeficiency virus (HIV) among pregnant women in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Lima, Lyana Rodrigues Pinto; Fernandes, Luis Eduardo Barros Costa; Villela, Daniel A M; Morgado, Mariza Gonçalves; Pilotto, José Henrique; de Paula, Vanessa Salete

    2018-03-01

    Pregnant women who are infected with the Human Immunodeficiency Virus (HIV) are particularly vulnerable to severe and recurrent infections with Human Herpesvirus 2 (HHV-2). Neonatal transmission of HHV-2 has been associated with malformations and neurological sequelae in infants, which makes it very important to perform antenatal monitoring for genital herpes. In the study, 134 pregnant women infected with HIV were tested for HHV-2 IgM and IgG using an enzyme-linked immunosorbent assay (ELISA) and had HHV-2 DNA analyzed by Real Time Polymerase Chain Reaction (qPCR). Fisher's exact test was applied to analyze the epidemiological dates (p pregnant women infected with HIV had HHV-2 IgG and 3.75% of them showed HHV-2 viremia. HHV-2 IgM was found in 6% of the pregnant women and 25% of them had HHV-2 viremia. The risk factors associated with HHV-2 seropositive were age under 20 and a CD4/CD8 ratio > 1. Our study found high HHV-2/HIV coinfection prevalence and HHV-2 viremia among patients with recurrent and primary genital infection, reinforcing the need of prevention and control of HHV-2 infection in order to avoid this virus transmission.

  12. Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

    Science.gov (United States)

    Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

    2017-05-01

    Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. T-cell immunity to herpesviruses in immune disorders

    NARCIS (Netherlands)

    Scherrenburg, J.

    2009-01-01

    Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) are wide-spread herpesviruses, which establish life-long persistence in the host upon primary infection. Primary infection with herpesviruses causes usually only mild symptoms, however in some situations, such as during immunosuppression or human

  14. Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants.

    Directory of Open Access Journals (Sweden)

    Anabel S de la Garza-Rodea

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID mice could be attained provided that recipients' natural killer (NK cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable.

  15. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  16. Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration.

    Science.gov (United States)

    Engdahl, Elin; Dunn, Nicky; Niehusmann, Pitt; Wideman, Sarah; Wipfler, Peter; Becker, Albert J; Ekström, Tomas J; Almgren, Malin; Fogdell-Hahn, Anna

    2017-06-01

    Human herpesvirus 6B (HHV-6B) is a neurotropic betaherpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with an Illumina 450K array, comparing HHV-6B-infected and uninfected Molt-3 T cells 3 days postinfection. Bisulfite pyrosequencing was used to validate the Illumina results and to investigate methylation over time in vitro Expression of genes was investigated using quantitative PCR (qPCR), and virus integration was investigated with PCR. A total of 406 CpG sites showed a significant HHV-6B-induced change in methylation in vitro Remarkably, 86% (351/406) of these CpGs were located integration in Molt-3 cell DNA 3 days after infection. The telomere at 17p has repeatedly been described as an integration site for HHV-6B, and we show for the first time that HHV-6B induces hypomethylation in this region during acute infection, which may play a role in the integration process, possibly by making the DNA more accessible. IMPORTANCE The ability to establish latency in the host is a hallmark of herpesviruses, but the mechanisms differ. Human herpesvirus 6B (HHV-6B) is known to establish latency through integration of its genome into the telomeric regions of host cells, with the ability to reactivate. Our study is the first to show that HHV-6B specifically induces hypomethylated regions close to the telomeres and that integrating viruses may use the host methylation machinery to facilitate their integration process. The results from this study contribute to knowledge of HHV-6B biology and virus-host interaction. This in turn will lead to further progress in our understanding of the underlying mechanisms by which HHV-6B contributes to pathological processes and may have important implications in both disease prevention and treatment. Copyright © 2017 American

  17. Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes

    Directory of Open Access Journals (Sweden)

    Christian Eaton

    2011-01-01

    Full Text Available Kaposi sarcoma (KS, multicentric Castleman's disease (MCD, and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8 infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.

  18. Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Nagamata, Satoshi; Nagasaka, Miwako; Kawabata, Akiko; Kishimoto, Kenji; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Mori, Takeshi; Morioka, Ichiro; Nishimura, Noriyuki; Iijima, Kazumoto; Yamada, Hideto; Kawamoto, Shinichiro; Yakushijin, Kimikazu; Matsuoka, Hiroshi; Mori, Yasuko

    2018-05-01

    CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4 + and CD8 + cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4 + T cells, p = .02 in CD8 + T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4 + T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Human parvovirus B19, varicella zoster virus, and human herpesvirus-6 in mesenchymal stem cells of patients with osteoarthritis: analysis with quantitative real-time polymerase chain reaction.

    Science.gov (United States)

    Rollín, R; Alvarez-Lafuente, R; Marco, F; Jover, J A; Hernández-García, C; Rodríguez-Navas, C; López-Durán, L; Fernández-Gutiérrez, B

    2007-04-01

    To investigate whether there is a possible viral transmission using mesenchymal stem cells (MSCs) in autologous or allogeneic transplantation in the context of osteoarthritis (OA) patients. The presence of parvovirus B19 (B19), varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6) was studied in MSCs from bone marrow of patients with OA and healthy controls. MSCs were prepared from bone marrow aspirates obtained from 18 patients undergoing joint replacement as a result of OA and from 10 healthy controls. DNA was extracted from primary MSCs' culture established from these cells and quantitative real-time polymerase chain reaction was performed to analyse the prevalence and viral load of B19, VZV and HHV-6. The prevalence of total viral DNA among patients with OA was 16.7% (3/18), with a mean viral load of 29.7 copies/microg of DNA. One out of 18 was positive for B19 (viral load, 61.2 copies/microg of DNA), two for VZV (mean viral load, 14.4 copies/microg of DNA), and none for HHV-6. The prevalence of total viral DNA in the control group was 20% (2/10), with a mean viral load of 13.4 copies/microg of DNA. Both positive results were of B19 parvoviruses. There were no statistically significant differences among patients and controls. This first approach to the viral prevalence in MSCs of bone marrow in OA patients and healthy controls seems to show a very low risk of viral transmission or reactivation in a possible MSCs' transplantation.

  20. Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State

    Directory of Open Access Journals (Sweden)

    Souza V.A.U.F.

    2004-01-01

    Full Text Available Human herpesvirus 8 (HHV-8 is a newly described herpesvirus that is etiologically associated with all forms of Kaposi's sarcoma (KS. Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies among men who have sex with men (MSM and AIDS patients, African children, Brazilian Amerindians, and elderly individuals in certain regions of Europe. The aim of the present study was to determine the prevalence of HHV-8 antibodies in healthy children and young adults from different cities in São Paulo State, and in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS patients with and without KS. Antibodies to HHV-8 latency-associated nuclear antigen and lytic-phase antigens were detected by immunofluorescence assays. In 643 healthy children and young adults from the general population attending a vaccination program for yellow fever in ten different cities in São Paulo State, the prevalence of HHV-8 antibodies detected by the presence of latent or lytic antigens ranged from 1.0 to 4.1% in the different age groups (mean = 2.5%. In the MSM group, the prevalence was 31/95 (32.6%. In the group of patients with AIDS, the prevalence was 39.2% (51/130 for non-KS patients and 98.7% (77/78 for AIDS patients with the diagnosis of KS confirmed by histopathological examination. We conclude that HHV-8 has a restricted circulation among healthy children and young adults in the general population of São Paulo State and a high prevalence among MSM and AIDS patients.

  1. Is the drug-induced hypersensitivity syndrome (DIHS due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

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    Borgia Guglielmo

    2010-03-01

    Full Text Available Abstract Background Drug-Induced Hypersensitivity Syndrome (DIHS is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug. We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. Case presentation We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6 DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die that was tapered very slowly. The patient recovered completely. Conclusions The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.

  2. Human herpesvirus-8 (HHV-8 antibodies in women from São Paulo, Brazil: association with behavioral factors and Kaposi's sarcoma

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    Caterino-de-Araujo Adele

    2003-01-01

    Full Text Available BACKGROUND: With the spread of AIDS, many HIV-infected women have been diagnosed with Kaposi's sarcoma (KS, especially in Africa. Since the discovery of a novel herpesvirus as the causative agent of KS (human herpesvirus 8 - HHV-8 several seroepidemiological studies have been conducted to identify groups at risk for KS. The risk for women in Brazil has not been studied. MATERIALS AND METHODS: We searched for HHV-8 antibodies in sera obtained from a bank made up of samples from 3 groups of individuals: Group I: 163 HIV-1-infected women attended at an ambulatory clinic in 1994; Group II: 108 children born to HIV-1-infected mothers from 1990 to 1992, their antibodies reflected maternal infection, and Group III: 630 HIV-1-seronegative, healthy women. In-house immunofluorescence and Western-Blot assays based on the BCBL-1 cell line were used to detect anti-latent and anti-lytic HHV-8 antibodies. RESULTS: Group I had an overall frequency of antibodies of 8.6%, with a 1.2% frequency of anti-latent antibodies and an 8.0% frequency of anti-lytic antibodies. Similar results were detected in Group II, i.e., no cases with anti-latent antibodies and a 7.4% frequency of anti-lytic antibodies. In contrast, prevalences of 1.1% anti-latent antibodies and 0.3% anti-lytic antibodies were observed in Group III. CONCLUSIONS: The epidemiologic pattern of HHV-8 in women from São Paulo varies according to behavioral factors, with emphasis on the sexual and blood routes of virus transmission/acquisition. Although HHV-8 anti-lytic antibodies were found in HIV-1-infected women, no case of KS was detected. Protective factors against KS are probably related to gender and/or to antiretroviral therapies introduced in Brazil since 1994.

  3. Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K-bZIP)

    International Nuclear Information System (INIS)

    AuCoin, David P.; Colletti, Kelly S.; Cei, Sylvia A.; Papouskova, Iva; Tarrant, Margaret; Pari, Gregory S.

    2004-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has significant sequence homology to Epstein-Barr virus (EBV). In cell culture, HHV8 is primarily latent, and viral genes associated with lytic replication are not expressed. Two lytic origins of DNA replication (oriLyt) are present within the HHV8 genome and are composed of an AT-rich region adjacent to GC-rich DNA sequences. We have now identified essential cis- and trans-acting elements required for oriLyt-dependent DNA replication. The transient replication assay was used to show that two AT-rich elements, three consensus AP1 transcription factor-binding sites, an ORF50 response element (RE), and a consensus TATA box motif are essential for efficient origin-dependent DNA replication. Transient transfection of luciferase reporter constructs indicated that the downstream region of the HHV8 oriLyt responds to ORF50 and suggests that part of the oriLyt may be an enhancer/promoter. In addition, a transient cotransfection-replication assay elucidated the set of trans-acting factors required for lytic DNA replication. These factors consist of homologues to the core replication proteins: ORF6 (ssDNA binding protein), ORF9 (DNA polymerase), ORF40-41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and ORF59 (polymerase processivity factor) common to all herpesviruses along with ORF50 (K-Rta) and K8 (K-bZIP)

  4. Bioactive activities of natural products against herpesvirus infection.

    Science.gov (United States)

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

  5. A Simple Proteomics-Based Approach to Identification of Immunodominant Antigens from a Complex Pathogen: Application to the CD4 T Cell Response against Human Herpesvirus 6B.

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    Aniuska Becerra-Artiles

    Full Text Available Most of humanity is chronically infected with human herpesvirus 6 (HHV-6, with viral replication controlled at least in part by a poorly characterized CD4 T cell response. Identification of viral epitopes recognized by CD4 T cells is complicated by the large size of the herpesvirus genome and a low frequency of circulating T cells responding to the virus. Here, we present an alternative to classical epitope mapping approaches used to identify major targets of the T cell response to a complex pathogen like HHV-6B. In the approach presented here, extracellular virus preparations or virus-infected cells are fractionated by SDS-PAGE, and eluted fractions are used as source of antigens to study cytokine responses in direct ex vivo T cell activation studies. Fractions inducing significant cytokine responses are analyzed by mass spectrometry to identify viral proteins, and a subset of peptides from these proteins corresponding to predicted HLA-DR binders is tested for IFN-γ production in seropositive donors with diverse HLA haplotypes. Ten HHV-6B viral proteins were identified as immunodominant antigens. The epitope-specific response to HHV-6B virus was complex and variable between individuals. We identified 107 peptides, each recognized by at least one donor, with each donor having a distinctive footprint. Fourteen peptides showed responses in the majority of donors. Responses to these epitopes were validated using in vitro expanded cells and naturally expressed viral proteins. Predicted peptide binding affinities for the eight HLA-DRB1 alleles investigated here correlated only modestly with the observed CD4 T cell responses. Overall, the response to the virus was dominated by peptides from the major capsid protein U57 and major antigenic protein U11, but responses to other proteins including glycoprotein H (U48 and tegument proteins U54 and U14 also were observed. These results provide a means to follow and potentially modulate the CD4 T-cell immune

  6. Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

    DEFF Research Database (Denmark)

    Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

    2008-01-01

    Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...... transactivated the RANTES promoter. Mutational analysis of the promoter indicated that transactivation was not critically dependent on the promoter sites CRE, NF-kappaB, ISRE or NF-IL6. ND10 are nuclear substructures that are involved in several cellular regulatory pathways, including those controlling gene...... structure, U19 also localized to the centre of ND10. Knockdown of PML by small interfering RNA did not prevent U19 localization to ND10-like foci, but instead led to a fourfold increase in U19-induced transcription from the RANTES promoter. Generation of four truncated U19 proteins indicated that the N...

  7. Neuroimaging of herpesvirus infections in children

    Energy Technology Data Exchange (ETDEWEB)

    Baskin, Henry J. [Cincinnati Children' s Medical Center, Department of Radiology, Cincinnati, OH (United States); Hedlund, Gary [Primary Children' s Medical Center, Department of Medical Imaging, Salt Lake City, UT (United States)

    2007-10-15

    Six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster (VZV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6). When herpesviruses infect the central nervous system (CNS), the clinical presentation is non-specific and often confounding. The clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagnosis and treatment rely heavily on neuroimaging. This review focuses on the spectrum of cerebral manifestations caused by these viruses, particularly on non-congenital presentations. Recent advances in our understanding of these viruses are discussed, including new polymerase chain reaction techniques that allow parallel detection, which has improved our recognition that the herpesviruses are neurotropic and involve the CNS more often than previously thought. Evolving knowledge has also better elucidated viral neuropathology, particularly the role of VZV vasculitis in the brain, HHV-6 in febrile seizures, and herpesvirus reactivation in immunosuppressed patients. The virology, clinical course, and CNS manifestations of each virus are reviewed, followed by descriptions of neuroimaging findings when these agents infect the brain. Characteristic but often subtle imaging findings are discussed, as well as technical pearls covering appropriate use of MRI and MRI adjuncts to help differentiate viral infection from mimics. (orig.)

  8. Neuroimaging of herpesvirus infections in children

    International Nuclear Information System (INIS)

    Baskin, Henry J.; Hedlund, Gary

    2007-01-01

    Six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster (VZV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6). When herpesviruses infect the central nervous system (CNS), the clinical presentation is non-specific and often confounding. The clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagnosis and treatment rely heavily on neuroimaging. This review focuses on the spectrum of cerebral manifestations caused by these viruses, particularly on non-congenital presentations. Recent advances in our understanding of these viruses are discussed, including new polymerase chain reaction techniques that allow parallel detection, which has improved our recognition that the herpesviruses are neurotropic and involve the CNS more often than previously thought. Evolving knowledge has also better elucidated viral neuropathology, particularly the role of VZV vasculitis in the brain, HHV-6 in febrile seizures, and herpesvirus reactivation in immunosuppressed patients. The virology, clinical course, and CNS manifestations of each virus are reviewed, followed by descriptions of neuroimaging findings when these agents infect the brain. Characteristic but often subtle imaging findings are discussed, as well as technical pearls covering appropriate use of MRI and MRI adjuncts to help differentiate viral infection from mimics. (orig.)

  9. Human herpesvirus-8 (HHV-8 sero-detection and HIV association in Kaposi's sarcoma (KS, non-KS tumors and non-neoplastic conditions

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    Pak Fatemeh

    2008-06-01

    Full Text Available Abstract Background The association of the human herpesvirus-8/Kaposi's sarcoma (KS-associated herpesvirus (HHV-8/KSHV serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA. Selected archival diagnostic biopsies (n = 184 and sera from indigenous patients with KS (n = 120, non-KS tumors (n = 24 and non-neoplastic lesions (n = 40 at Muhimbili National Hospital (MNH, Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA] and serology for HIV (ELISA and HHV-8 (IFA and ELISA. Results About 66.3% (n = 122 cases including AIDS-associated Kaposi's sarcoma (AKS (n = 93, reactive conditions (n = 28 and only one non-KS tumour were HIV positive. Endemic KS (EKS patients were mostly males (96.3%, 26/27 who were less (69.9%, 65/93 predominant in AIDS-associated (AKS. A high (89% percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92% cases, males (81.2%, KS patients (93%, non-KS tumors (92%, and reactive conditions (75%. All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively. Conclusion HHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of

  10. An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits.

    Science.gov (United States)

    Hayashi, K; Ohara, N; Teramoto, N; Onoda, S; Chen, H L; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yates, J; Akagi, T

    2001-04-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.

  11. Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

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    Miriam YH Ueda

    2015-06-01

    Full Text Available Human herpesvirus 6 (HHV-6 may cause severe complications after haematopoietic stem cell transplantation (HSCT. Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

  12. Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells

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    Ching-Yi Tsai

    2017-12-01

    Full Text Available Epigallocatechin-3-gallate (EGCG, the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL is an aggressive neoplasm caused by human herpesvirus 8 (HHV8. In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas.

  13. Attempt of differentiation acute encephalopathy with febrile convulsive status epilepticus from febrile convulsive status epilepticus induced by human herpesvirus 6 at early stage

    International Nuclear Information System (INIS)

    Ishikawa, Junichi; Yamamuro, Miho; Togawa, Masao; Shiomi, Masashi

    2010-01-01

    It is difficult for clinicians to predict the subsequent development of acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), when febrile convulsive status epilepticus (FCSE) develops. Comparing clinical and laboratory characteristics between patients with AEFCSE and those with FCSE, we investigated the factors which predict the later development of febrile convulsive status caused by human herpesvirus 6 (HHV6). The subjects of this study were patients treated for FCSE or AEFCSE due to HHV6 in our hospital between April 2004 and January 2008. The AEFCSE group included 5 patients, and the FCSE group included 6 patients. There were few differences in clinical characteristics or brain images on admission between the 2 groups. Disturbance of consciousness persisted for 24 hours or more in all patients in the AEFCSE group and in 2 patients in the FCSE group. The serum creatinine concentration was significantly higher in the AEFCSE group. Serum creatinine concentration could be a good indicator for the prediction of AEFCSE in patients with FCSE. (author)

  14. Attempt of differentiation acute encephalopathy with febrile convulsive status epilepticus from febrile convulsive status epilepticus induced by human herpesvirus 6 at early stage

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Junichi; Yamamuro, Miho; Togawa, Masao; Shiomi, Masashi [Osaka City General Hospital, Osaka, Osaka (Japan)

    2010-07-15

    It is difficult for clinicians to predict the subsequent development of acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), when febrile convulsive status epilepticus (FCSE) develops. Comparing clinical and laboratory characteristics between patients with AEFCSE and those with FCSE, we investigated the factors which predict the later development of febrile convulsive status caused by human herpesvirus 6 (HHV6). The subjects of this study were patients treated for FCSE or AEFCSE due to HHV6 in our hospital between April 2004 and January 2008. The AEFCSE group included 5 patients, and the FCSE group included 6 patients. There were few differences in clinical characteristics or brain images on admission between the 2 groups. Disturbance of consciousness persisted for 24 hours or more in all patients in the AEFCSE group and in 2 patients in the FCSE group. The serum creatinine concentration was significantly higher in the AEFCSE group. Serum creatinine concentration could be a good indicator for the prediction of AEFCSE in patients with FCSE. (author)

  15. MicroRNAs in large herpesvirus DNA genomes: recent advances.

    Science.gov (United States)

    Sorel, Océane; Dewals, Benjamin G

    2016-08-01

    MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that regulate gene expression. They alter mRNA translation through base-pair complementarity, leading to regulation of genes during both physiological and pathological processes. Viruses have evolved mechanisms to take advantage of the host cells to multiply and/or persist over the lifetime of the host. Herpesviridae are a large family of double-stranded DNA viruses that are associated with a number of important diseases, including lymphoproliferative diseases. Herpesviruses establish lifelong latent infections through modulation of the interface between the virus and its host. A number of reports have identified miRNAs in a very large number of human and animal herpesviruses suggesting that these short non-coding transcripts could play essential roles in herpesvirus biology. This review will specifically focus on the recent advances on the functions of herpesvirus miRNAs in infection and pathogenesis.

  16. Herpesviruses and breast milk

    OpenAIRE

    C. Pietrasanta; B. Ghirardi; M.F. Manca; S. Uccella; C. Gualdi; E. Tota; L. Pugni; F. Mosca

    2014-01-01

    Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections ar...

  17. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells.

    Science.gov (United States)

    Watanabe, Takahiro; Sugaya, Makoto; Atkins, April M; Aquilino, Elisabeth A; Yang, Aparche; Borris, Debra L; Brady, John; Blauvelt, Andrew

    2003-06-01

    Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen (LANA) and k-cyclin (kCYC). To assess the oncogenic potential of LANA and kCYC, primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen (LTAg). Interestingly, LANA-transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean +/- standard deviation, 38.3 +/- 11.0 passages) than untransduced cells and vector-transduced cells (<20 passages). By contrast, kCYC-transduced HUVEC did not proliferate faster or live longer than control cells. LANA- and kCYC-transduced HUVEC, but not LTAg-transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA- and kCYC-transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg-transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA-transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA-expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.

  18. Human herpesvirus 8 (HHV-8 detected by nested polymerase chain reaction (PCR in HIV patients with or without Kaposi's sarcoma. An analytic cross-sectional study

    Directory of Open Access Journals (Sweden)

    Paula Renata Lima Machado

    Full Text Available CONTEXT AND OBJECTIVE: Kaposi's sarcoma (KS is a common neoplastic disease in AIDS patients. The aim of this study was to evaluate the frequency of human herpesvirus 8 (HHV-8 infection in human immunodeficiency virus (HIV-infected patients, with or without KS manifestations and correlate HHV-8 detection with KS staging. DESIGN AND SETTING: Analytic cross-sectional study conducted in a public tertiary-level university hospital in Ribeirão Preto, São Paulo, Brazil. METHODS: Antibodies against HHV-8 lytic-phase antigens were detected by means of the immunofluorescence assay. HHV-8 DNA was detected in the patient samples through a nested polymerase chain reaction (nested PCR that amplified a region of open reading frame (ORF-26 of HHV-8. RESULTS: Anti-HHV-8 antibodies were detected in 30% of non-KS patients and 100% of patients with KS. Furthermore, the HHV-8 DNA detection rates observed in HIV-positive patients with KS were 42.8% in serum, 95.4% in blood samples and 100% in skin biopsies; and in patients without KS, the detection rate was 4% in serum. Out of the 16 serum samples from patients with KS-AIDS who were classified as stage II, two were positive (12.5%; and out of the 33 samples from patients in stage IV, 19 (57.6% were positive. CONCLUSION: We observed an association between HHV-8 detection and disease staging, which was higher in the serum of patients in stage IV. This suggests that detection of HHV-8 DNA in serum could be very useful for clinical assessment of patients with KS and for monitoring disease progression.

  19. HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B.

    Science.gov (United States)

    Collin, Vanessa; Flamand, Louis

    2017-06-26

    Unlike other human herpesviruses, human herpesvirus 6A and 6B (HHV-6A/B) infection can lead to integration of the viral genome in human chromosomes. When integration occurs in germinal cells, the integrated HHV-6A/B genome can be transmitted to 50% of descendants. Such individuals, carrying one copy of the HHV-6A/B genome in every cell, are referred to as having inherited chromosomally-integrated HHV-6A/B (iciHHV-6) and represent approximately 1% of the world's population. Interestingly, HHV-6A/B integrate their genomes in a specific region of the chromosomes known as telomeres. Telomeres are located at chromosomes' ends and play essential roles in chromosomal stability and the long-term proliferative potential of cells. Considering that the integrated HHV-6A/B genome is mostly intact without any gross rearrangements or deletions, integration is likely used for viral maintenance into host cells. Knowing the roles played by telomeres in cellular homeostasis, viral integration in such structure is not likely to be without consequences. At present, the mechanisms and factors involved in HHV-6A/B integration remain poorly defined. In this review, we detail the potential biological and medical impacts of HHV-6A/B integration as well as the possible chromosomal integration and viral excision processes.

  20. p130Cas scaffolds the signalosome to direct adaptor-effector cross talk during Kaposi's sarcoma-associated herpesvirus trafficking in human microvascular dermal endothelial cells.

    Science.gov (United States)

    Bandyopadhyay, Chirosree; Veettil, Mohanan Valiya; Dutta, Sujoy; Chandran, Bala

    2014-12-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface receptors, such as heparan sulfate, integrins (α3β1, αVβ3, and αVβ5), and EphrinA2 (EphA2), and activates focal adhesion kinase (FAK), Src, phosphoinositol 3-kinase (PI3-K), c-Cbl, and RhoA GTPase signal molecules early during lipid raft (LR)-dependent productive macropinocytic entry into human dermal microvascular endothelial cells. Our recent studies have identified CIB1 as a signal amplifier facilitating EphA2 phosphorylation and subsequent cytoskeletal cross talk during KSHV macropinocytosis. Although CIB1 lacks an enzymatic activity and traditional adaptor domain or known interacting sequence, it associated with the KSHV entry signal complex and the CIB1-KSHV association was sustained over 30 min postinfection. To identify factors scaffolding the EphA2-CIB1 signal axis, the role of major cellular scaffold protein p130Cas (Crk-associated substrate of Src) was investigated. Inhibitor and small interfering RNA (siRNA) studies demonstrated that KSHV induced p130Cas in an EphA2-, CIB1-, and Src-dependent manner. p130Cas and Crk were associated with KSHV, LRs, EphA2, and CIB1 early during infection. Live-cell microscopy and biochemical studies demonstrated that p130Cas knockdown did not affect KSHV entry but significantly reduced productive nuclear trafficking of viral DNA and routed KSHV to lysosomal degradation. p130Cas aided in scaffolding adaptor Crk to downstream guanine nucleotide exchange factor phospho-C3G possibly to coordinate GTPase signaling during KSHV trafficking. Collectively, these studies demonstrate that p130Cas acts as a bridging molecule between the KSHV-induced entry signal complex and the downstream trafficking signalosome in endothelial cells and suggest that simultaneous targeting of KSHV entry receptors with p130Cas would be an attractive potential avenue for therapeutic intervention in KSHV infection. Eukaryotic cell adaptor molecules, without any intrinsic

  1. Human herpesvirus infections of the central nervous system: laboratory diagnosis based on DNA detection by nested PCR in plasma and cerebrospinal fluid samples.

    Science.gov (United States)

    Rimério, Carla Aparecida Tavares; De Oliveira, Renato Souza; de Almeida Bonatelli, Murilo Queiroz; Nucci, Anamarli; Costa, Sandra Cecília Botelho; Bonon, Sandra Helena Alves

    2015-04-01

    Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the "gold standard," and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture. © 2015 Wiley Periodicals, Inc.

  2. A single tube PCR assay for simultaneous amplification of HSV-1/-2, VZV, CMV, HHV-6A/-6B, and EBV DNAs in cerebrospinal fluid from patients with virus-related neurological diseases.

    Science.gov (United States)

    Yamamoto, T; Nakamura, Y

    2000-10-01

    Cerebrospinal fluid (CSF) specimens from 27 patients with encephalitis, meningitis, and other neurological diseases were studied for the presence of herpes simplex virus types 1 and 2 (HSV-1/-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesviruses 6A and 6B (HHV-6A/-6B) and Epstein-Barr virus (EBV) DNA using the polymerase chain reaction (PCR) method. The DNAs were amplified using two sets of consensus primer pairs in a single tube, bringing simultaneous amplification of the herpesviruses. The PCR products were analyzed by agarose gel electrophoresis, and Southern blot hybridization with virus-type specific probes, thus allowing discrimination between the different types of herpesviruses to be made. Each virus-specific probe was highly specific for identifying the PCR product. Thirty CSF specimens from 13 patients with encephalitis and 10 specimens from 10 patients with meningitis, respectively, were examined using this method. Eight patients with encephalitis and six with meningitis were positive for different herpesviruses, including patients with coinfections (HSV-1/-2 and VZV, VZV and CMV). Among four CSF specimens from four patients with other neurological disorders, dual amplification of CMV and EBV was present. Since identification of the types of herpesviruses in this system requires a very small amount of CSF, and is completed with one PCR, it is useful for routine diagnosis of herpesvirus infections in diagnostic laboratories. The viruses responsible for central nervous system infection are easily detected with various coinfection and serial patterns of herpesviruses, by this consensus primer-based PCR method. This may give an insight into the relationship between virus-related neurological diseases (VRNDS) and herpesvirus infections.

  3. Bovine herpesvirus 1 interferes with TAP-dependent peptide transport and intracellular trafficking of MHC class I molecules in human cells

    NARCIS (Netherlands)

    Koppers-Lalic, D.; Rychlowski, M.; Leeuwen, D.; Rijsewijk, F.A.M.; Ressing, M.E.; Neefjes, J.J.; Bienkowska-Szewczyk, K.; Wiertz, E.

    2003-01-01

    Bovine herpesvirus 1 (BoHV-1), the cause of infectious bovine rhinotracheitis and infectious pustular vulvovaginitis in cattle, establishes a lifelong infection, despite the presence of antiviral immunity in the host. BoHV-1 has been shown to elude the host immune system, but the viral gene products

  4. Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2006-01-01

    -associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env...

  5. Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2007-01-01

    -associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env...

  6. Human herpesvirus 8 (HHV-8 and the etiopathogenesis of Kaposi's sarcoma Herpesvírus humano tipo 8 (HHV-8 e a etiopatogênese do sarcoma de Kaposi

    Directory of Open Access Journals (Sweden)

    Jair Carneiro Leão

    2002-08-01

    Full Text Available OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.OBJETIVO: O objetivo do presente artigo foi revisar a literatura recente em rela

  7. Dissecting the host response to a gamma-herpesvirus

    DEFF Research Database (Denmark)

    Doherty, P C; Christensen, Jan Pravsgaard; Belz, G T

    2001-01-01

    The murine gamma-herpesvirus 68 (MHV-68) provides a unique experimental model for dissecting immunity to large DNA viruses that persist in B lymphocytes. The analysis is greatly facilitated by the availability of genetically disrupted (-/-) mice that lack key host-response elements, and by the fact...... cells, which is apparently MHC independent, could represent some sort of 'smoke screen' used by MHV-68 to subvert immunity. Although MHV-68 is neither Epstein-Barr virus nor human herpesvirus-8, the results generated from this system suggest possibilities that may usefully be addressed with these human...

  8. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  9. HERPESVIRUS INFECTIONS: MYTHS AND REALITIES

    Directory of Open Access Journals (Sweden)

    Makarenko VD

    2015-04-01

    Full Text Available millennia, and its main symptoms described by Hippocrates more. But our time HVI remains mysterious and before the end of the unknown. Among the issues are not sufficiently clarified latency of infection and persistence of herpes viruses, the causes of the frequent occurrence of the disease in the form of subclinical forms, high infection rate of the world population, and others. Note that virologists and clinicians are showing in the last 20 years to the HVI, is associated with a variety of everincreasing role Herpesviridae in infectious pathology of human and social importance of diseases caused by them. It is now known 8 herpesviruses pathogenic for humans. Because of the difference in a number of biological properties, the nature of replication in cell cultures, the clinical picture and the pathogenesis of diseases caused by all herpesviruses are distributed according to the recommendations of the International Committee on Taxonomy of Viruses, in three subfamilies (α, β, γ. Activators of herpes simplex virus can be endogenous and exogenous factors: reduction of immunoreactivity of the organism (immunodeficiency, interferon failure, physical and emotional stress, overheating or overcooling, hormonal disorders, ultraviolet irradiation, corticosteroids treatment, cytotoxic drugs. It is important to understand that the HVI is a disease of the whole body with lesions in varying degrees, all organs and systems (immune, hematopoietic, lymphatic, CNS, which is responsible for the homeostasis of the human body. These data give reason to believe HVI systemic disease, mainly affecting a particular organ. However, more is still not widely used etiopathogenetical and "topical" diagnosis, indicating the loss of any one body. Due to the fact that the clinical forms of HVI are characterized by marked polymorphism, the timely establishment of the etiologic diagnosis is a difficult task and is based on the use of specific molecular genetic, virological

  10. An unusual dependence of human herpesvirus-8 Glycoproteins-induced cell-to-cell fusion on heparan sulfate

    Science.gov (United States)

    Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

    2009-01-01

    Human herpes virus 8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: 1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; 2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, 3) coexpression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis. PMID:19747451

  11. A neurotropic herpesvirus infecting the gastropod, abalone, shares ancestry with oyster herpesvirus and a herpesvirus associated with the amphioxus genome

    Directory of Open Access Journals (Sweden)

    Sawbridge Tim

    2010-11-01

    Full Text Available Abstract Background With the exception of the oyster herpesvirus OsHV-1, all herpesviruses characterized thus far infect only vertebrates. Some cause neurological disease in their hosts, while others replicate or become latent in neurological tissues. Recently a new herpesvirus causing ganglioneuritis in abalone, a gastropod, was discovered. Molecular analysis of new herpesviruses, such as this one and others, still to be discovered in invertebrates, will provide insight into the evolution of herpesviruses. Results We sequenced the genome of a neurotropic virus linked to a fatal ganglioneuritis devastating parts of a valuable wild abalone fishery in Australia. We show that the newly identified virus forms part of an ancient clade with its nearest relatives being a herpesvirus infecting bivalves (oyster and, unexpectedly, one we identified, from published data, apparently integrated within the genome of amphioxus, an invertebrate chordate. Predicted protein sequences from the abalone virus genome have significant similarity to several herpesvirus proteins including the DNA packaging ATPase subunit of (putative terminase and DNA polymerase. Conservation of amino acid sequences in the terminase across all herpesviruses and phylogenetic analysis using the DNA polymerase and terminase proteins demonstrate that the herpesviruses infecting the molluscs, oyster and abalone, are distantly related. The terminase and polymerase protein sequences from the putative amphioxus herpesvirus share more sequence similarity with those of the mollusc viruses than with sequences from any of the vertebrate herpesviruses analysed. Conclusions A family of mollusc herpesviruses, Malacoherpesviridae, that was based on a single virus infecting oyster can now be further established by including a distantly related herpesvirus infecting abalone, which, like many vertebrate viruses is neurotropic. The genome of Branchiostoma floridae (amphioxus provides evidence for the

  12. The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; McLean, Katherine A; Holst, Peter J

    2004-01-01

    Open reading frame 74 (ORF74) of many gamma(2)-herpesviruses encodes a CXC chemokine receptor. The molecular pharmacological profile of ORF74 from herpesvirus saimiri, ECRF3, is characterized here and compared with that of the well known ORF74 from human herpesvirus 8 (HHV8). The ECRF3 receptor...... ligand selectivity of ECRF3 among ORF74 receptors could reflect differences in the cellular tropism of the gamma(2)-herpesviruses....

  13. Recent advances in understanding Kaposi’s sarcoma-associated herpesvirus [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Nathan J. Dissinger

    2016-04-01

    Full Text Available Kaposi’s sarcoma (KS-associated herpesvirus (KSHV is an oncogenic human herpesvirus. KSHV is associated with three cancers in the human population: KS, primary effusion lymphoma (PEL, and multicentric Castleman’s disease (MCD. KS is the leading cause of cancer in HIV-infected individuals. In this review, we discuss the most recent discoveries behind the mechanisms of KSHV latency maintenance and lytic replication. We also review current therapies for KSHV-associated cancers.

  14. Herpesviruses and breast milk.

    Science.gov (United States)

    Pietrasanta, C; Ghirardi, B; Manca, M F; Uccella, S; Gualdi, C; Tota, E; Pugni, L; Mosca, F

    2014-06-30

    Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP) does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

  15. Herpesviruses and breast milk

    Directory of Open Access Journals (Sweden)

    C. Pietrasanta

    2014-06-01

    Full Text Available Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV and cytomegalovirus (CMV, herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

  16. Regulatory Role of N6 -methyladenosine (m6 A) Methylation in RNA Processing and Human Diseases.

    Science.gov (United States)

    Wei, Wenqiang; Ji, Xinying; Guo, Xiangqian; Ji, Shaoping

    2017-09-01

    N 6 -methyladenosine (m 6 A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m 6 A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m 6 A sites in single nucleotide resolution. Dynamic regulation of m 6 A is found in metabolism, embryogenesis, and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions. It has been known that m 6 A editing involves in nuclear RNA export, mRNA degradation, protein translation, and RNA splicing. Deficiency of m 6 A modification will lead to kinds of diseases, such as obesity, cancer, type 2 diabetes mellitus (T2DM), infertility, and developmental arrest. Some specific inhibitors against methyltransferase and demethylase have been developed to selectively regulate m 6 A modification, which may be advantageous for treatment of m 6 A related diseases. J. Cell. Biochem. 118: 2534-2543, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Phylodynamics of Merkel-cell polyomavirus and human polyomavirus 6: A long-term history with humans.

    Science.gov (United States)

    Torres, Carolina; Barrios, Melina Elizabeth; Cammarata, Robertina Viviana; Victoria, Matías; Fernandez-Cassi, Xavier; Bofill-Mas, Silvia; Colina, Rodney; Blanco Fernández, María Dolores; Mbayed, Viviana Andrea

    2018-04-20

    phylogenetic, epidemiological and historical data. Since a strong association is observed between the phylogenetic relationships and the origin of the sampled population, this analysis was based on the hypothesis of co-divergence between the virus and human populations. This analysis resulted in a substitution rate of 5.1 × 10 -8 s/s/y (∼5.1% of divergence per million years) for the complete genome of MCPyV, which is in the range of those estimated for other double-stranded DNA viruses. Regarding HPyV6, a South American group with clusterization was observed (sequences from Uruguay). Meanwhile, sequences from Argentina grouped with European ones (France and Spain) and remained separated from those isolated in China, USA or Australia. The analysis of viruses from the environment allowed us to deep characterize prevalent infections in different geographic regions, reveling that viruses circulating in each population reflected its origin and that there are specific lineages associated with South America. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. In vivo growth-restricted and reversible malignancy induced by Human Herpesvirus-8/ KSHV: a cell and animal model of virally induced Kaposi's sarcoma

    Science.gov (United States)

    Mutlu, Agata D'Agostino; Cavallin, Lucas E.; Vincent, Loïc; Chiozzini, Chiara; Eroles, Pilar; Duran, Elda M.; Asgari, Zahra; Hooper, Andrea T.; La Perle, Krista M. D.; Hilsher, Chelsey; Gao, Shou-Jiang; Dittmer, Dirk P.; Rafii, Shahin; Mesri, Enrique A.

    2007-01-01

    Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth-restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS. PMID:17349582

  19. The role of herpesviruses in ocular infections

    Directory of Open Access Journals (Sweden)

    Asim V Farooq

    2010-09-01

    Full Text Available Asim V Farooq1, Arpeet Shah1, Deepak Shukla21Department of Ophthalmology and Visual Sciences, 2Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USAAbstract: Ocular infections caused by herpesviruses are an important cause of morbidity. The majority of cases are believed to be associated with herpes simplex virus type-1 (HSV-1, although HSV-2, varicella zoster virus (VZV, cytomegalovirus (CMV and Epstein–Barr virus (EBV are also associated with various ocular diseases. The ability of some herpes viruses to infect various anatomic regions of the eye may be facilitated by entry processes that are cell-type specific, and in many cases may occur more frequently in the immunocompromised. The elimination of the role of herpesviruses in ocular disease remains elusive, as they often develop life-long latency in a large proportion of humans. Experimental vaccines for ocular HSV have shown some benefit in animal models, a result that has not been adequately demonstrated in clinical trials. Meanwhile, ocular involvement in VZV remains unpredictable, and CMV retinitis continues to be an important cause of blindness in those infected by HIV.Keywords: ocular herpes, viral entry, antivirals, epidemiology, seroprevalence, ocular lymphomas, viral vaccine

  20. Comparative Genomics of Carp Herpesviruses

    Science.gov (United States)

    Kurobe, Tomofumi; Gatherer, Derek; Cunningham, Charles; Korf, Ian; Fukuda, Hideo; Hedrick, Ronald P.; Waltzek, Thomas B.

    2013-01-01

    Three alloherpesviruses are known to cause disease in cyprinid fish: cyprinid herpesviruses 1 and 3 (CyHV1 and CyHV3) in common carp and koi and cyprinid herpesvirus 2 (CyHV2) in goldfish. We have determined the genome sequences of CyHV1 and CyHV2 and compared them with the published CyHV3 sequence. The CyHV1 and CyHV2 genomes are 291,144 and 290,304 bp, respectively, in size, and thus the CyHV3 genome, at 295,146 bp, remains the largest recorded among the herpesviruses. Each of the three genomes consists of a unique region flanked at each terminus by a sizeable direct repeat. The CyHV1, CyHV2, and CyHV3 genomes are predicted to contain 137, 150, and 155 unique, functional protein-coding genes, respectively, of which six, four, and eight, respectively, are duplicated in the terminal repeat. The three viruses share 120 orthologous genes in a largely colinear arrangement, of which up to 55 are also conserved in the other member of the genus Cyprinivirus, anguillid herpesvirus 1. Twelve genes are conserved convincingly in all sequenced alloherpesviruses, and two others are conserved marginally. The reference CyHV3 strain has been reported to contain five fragmented genes that are presumably nonfunctional. The CyHV2 strain has two fragmented genes, and the CyHV1 strain has none. CyHV1, CyHV2, and CyHV3 have five, six, and five families of paralogous genes, respectively. One family unique to CyHV1 is related to cellular JUNB, which encodes a transcription factor involved in oncogenesis. To our knowledge, this is the first time that JUNB-related sequences have been reported in a herpesvirus. PMID:23269803

  1. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, T; Christensen, T; Hansen, H J

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

  2. Detection of novel strains of cyprinid herpesvirus closely related to koi herpesvirus

    NARCIS (Netherlands)

    Engelsma, M.Y.; Way, K.; Dodge, M.J.; Voorbergen-Laarman, H.A.; Panzarin, V.M.; Abbadi, M.; El-Matbouli, M.; Skall, H.F.; Kahns, S.; Stone, D.M.

    2013-01-01

    Cyprinid herpesvirus 3 (CyHV-3) or koi herpesvirus (KHV) is a devastating virus of carp. Using generic primers for the DNA polymerase and the major capsid protein genes of cyprinid herpesviruses, nucleotide sequences divergent from previously described CyHV-3 were obtained. At least 3 novel groups

  3. Detection of novel strains of cyprinid herpesvirus closely related to koi herpesvirus

    DEFF Research Database (Denmark)

    Engelsma, Marc Y.; Way, Keith; Dodge, Melanie J.

    2013-01-01

    Cyprinid herpesvirus 3 (CyHV-3) or koi herpesvirus (KHV) is a devastating virus of carp. Using generic primers for the DNA polymerase and the major capsid protein genes of cyprinid herpesviruses, nucleotide sequences divergent from previously described CyHV-3 were obtained. At least 3 novel groups...

  4. Epidemiological situation of Herpesvirus infections in buffalo herds: Bubaline Herpesvirus1 or Bovine Herpesvirus1?

    Directory of Open Access Journals (Sweden)

    G.L. Autorino

    2010-02-01

    Full Text Available Information on the distribution and related epidemiological characteristics of herpesvirus infections, and in particular referring to Bovine Herpesvirus 1 (BoHV1 and Bubaline Herpesvirus 1 (BuHV1 in buffaloes, have to date not been reported. Different studies based on serological surveys and viral isolation describe the circulation of both infections in this species. The specific etiological attribution of the infections in sero-surveys can be uncertain because of antigenic cross-reactivity of these ruminant α-herpesvirus and therefore depends on the diagnostic techniques employed. For this , we proceeded in verifying the diffusion of the two infections in a buffalo population of Central Italy. The sample size for the number of herds to test was defined considering an expected prevalence > 20% and the number of heads to be tested within each herd was established using an expected prevalence of > 25% (absolute precision of 5%, with 95% confidence level. The 155 herds to test were those with no IBR vaccination history. A maximum of 15 random blood samples were collected within the >3 year age category. The same sampling criteria was adopted when cows were present on buffalo farms to study the possible role of this species. Through the combined use of gB-gE Elisa tests, we assigned a specific infection status, for the BuHV1 infection status (gB-pos/gE-neg, as confirmed by an experimental infection conducted by us inoculating buffaloes with the BuHV1 “strain Metzler”, and for the BoHV1 status (gBpos/ gE-pos as that observed for the infection in bovines. Prevalence of infection, based on the Elisa status of each animal, were estimated for the whole sample and within each herd. Furthermore, the selected farms were investigated for their numeric consistency, presence of bovines, occurrence of typical clinical herpesvirus disorders occurring during the year prior to sampling. The association of these factors with the infection status was verified

  5. New Rising Infection: Human Herpesvirus 6 Is Frequent in Myeloma Patients Undergoing Autologous Stem Cell Transplantation after Induction Therapy with Bortezomib

    Directory of Open Access Journals (Sweden)

    Netanel Horowitz

    2012-01-01

    Full Text Available Herpesvirus 6 (HHV-6 infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM patients undergoing autologous stem cell transplantation (ASCT after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD (; 66% or thalidomide-dexamethasone (TD (, 34% induction, together with melphalan 200 mg/m2 autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%, accounting for 35% of those screened; its incidence was 19.5% ( in the VD group versus 9.5% ( in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

  6. Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU).

    Science.gov (United States)

    Dreyfus, D H

    2016-02-01

    Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU. © 2015 British Society for Immunology.

  7. Overexpression and purification of U24 from human herpesvirus type-6 in E. coli: unconventional use of oxidizing environments with a maltose binding protein-hexahistine dual tag to enhance membrane protein yield

    Directory of Open Access Journals (Sweden)

    Straus Suzana K

    2011-06-01

    Full Text Available Abstract Background Obtaining membrane proteins in sufficient quantity for biophysical study and biotechnological applications has been a difficult task. Use of the maltose binding protein/hexahistidine dual tag system with E.coli as an expression host is emerging as a high throughput method to enhance membrane protein yield, solubility, and purity, but fails to be effective for certain proteins. Optimizing the variables in this system to fine-tune for efficiency can ultimately be a daunting task. To identify factors critical to success in this expression system, we have selected to study U24, a novel membrane protein from Human Herpesvirus type-6 with potent immunosuppressive ability and a possible role in the pathogenesis of the disease multiple sclerosis. Results We expressed full-length U24 as a C-terminal fusion to a maltose binding protein/hexahistidine tag and examined the effects of temperature, growth medium type, cell strain type, oxidizing vs. reducing conditions and periplasmic vs. cytoplasmic expression location. Temperature appeared to have the greatest effect on yield; at 37°C full-length protein was either poorly expressed (periplasm or degraded (cytoplasm whereas at 18°C, expression was improved especially in the periplasm of C41(DE3 cells and in the cytoplasm of oxidizing Δtrx/Δgor mutant strains, Origami 2 and SHuffle. Expression of the fusion protein in these strains were estimated to be 3.2, 5.3 and 4.3 times greater, respectively, compared to commonly-used BL21(DE3 cells. We found that U24 is isolated with an intramolecular disulfide bond under these conditions, and we probed whether this disulfide bond was critical to high yield expression of full-length protein. Expression analysis of a C21SC37S cysteine-free mutant U24 demonstrated that this disulfide was not critical for full-length protein expression, but it is more likely that strained metabolic conditions favour factors which promote protein expression. This

  8. Herpesvirus Evasion of Natural Killer Cells.

    Science.gov (United States)

    De Pelsmaeker, Steffi; Romero, Nicolas; Vitale, Massimo; Favoreel, Herman W

    2018-06-01

    Natural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and they produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity and by the myriad of reports describing herpesvirus NK cell evasion strategies. The latter is particularly obvious for cytomegaloviruses, but increasing evidence indicates that most, if not all, members of the herpesvirus family suppress NK cell activity to some extent. This review discusses the different NK cell evasion strategies described for herpesviruses and how this knowledge may translate to clinical applications. Copyright © 2018 American Society for Microbiology.

  9. RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines

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    Moela P

    2016-07-01

    Full Text Available Pontsho Moela, Lesetja Raymond Motadi Department of Biochemistry, North-West University, Potchefstroom, South Africa Abstract: Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients’ specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin-induced apoptosis by RBBP6 targeting suggests a promising tool for

  10. Kaposi’s Sarcoma-associated herpesvirus microRNAs

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    Eva eGottwein

    2012-05-01

    Full Text Available Kaposi’s Sarcoma-associated herpesvirus (KSHV is a human pathogenic -herpesvirus strongly associated with the development of Kaposi’s Sarcoma and B cell proliferative disorders, including primary effusion lymphoma (PEL. The identification and functional investigation of non-coding RNAs expressed by KSHV is a topic with rapidly emerging importance. KSHV miRNAs derived from 12 stem-loops located in the major latency locus have been the focus of particular attention. Recent studies describing the transcriptome-wide identification of mRNA targets of the KSHV miRNAs suggest that these miRNAs have evolved a highly complex network of interactions with the cellular and viral transcriptomes. Relatively few KSHV miRNA targets, however, have been characterized at a functional level. Here, our current understanding of KSHV miRNA expression, targets and function will be reviewed.

  11. Genomic organization of the canine herpesvirus US region.

    Science.gov (United States)

    Haanes, E J; Tomlinson, C C

    1998-02-01

    Canine herpesvirus (CHV) is an alpha-herpesvirus of limited pathogenicity in healthy adult dogs and infectivity of the virus appears to be largely limited to cells of canine origin. CHV's low virulence and species specificity make it an attractive candidate for a recombinant vaccine vector to protect dogs against a variety of pathogens. As part of the analysis of the CHV genome, the authors determined the complete nucleotide sequence of the CHV US region as well as portions of the flanking inverted repeats. Seven full open reading frames (ORFs) encoding proteins larger than 100 amino acids were identified within, or partially within the CHV US: cUS2, cUS3, cUS4, cUS6, cUS7, cUS8 and cUS9; which are homologs of the herpes simplex virus type-1 US2; protein kinase; gG, gD, gI, gE; and US9 genes, respectively. An eighth ORF was identified in the inverted repeat region, cIR6, a homolog of the equine herpesvirus type-1 IR6 gene. The authors identified and mapped most of the major transcripts for the predicted CHV US ORFs by Northern analysis.

  12. Koi herpesvirus disease in carp

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    Jeremić Svetlana

    2007-01-01

    Full Text Available A disease in the koi carp (Cyprinus carpio koi and the common carp (Cyprinus carpio carpio, caused by the herpesvirus and accompanied by a high mortality rate, has spread across numerous fish ponds all over the world since 1998, resulting in massive mortality and significant financial losses. The herpesvirus-like virus, called the koi herpesvirus (KHV has been isolated and identified from the koi and the common carp in the course of the incidences of massive mortalities. The first appearance of a disease with a high mortality in the common and the koi carp caused by the koi herpesvirus (KHV was described in 1998 in Israel and the United States of America (USA. Since that time, a large number of cases of outbreaks of this disease have been confirmed throughout the world, including the USA, Israel, and a large number of European countries. The deaths occurred seasonally, in late spring or early autumn, when the water temperature was from 18-28ºC. The most important factor of the environment that affects the occurrence and gravity of this disease is the water temperature. This disease is currently considered one of the factors that present the biggest threat to populations of the common and the koi carp. Diseased fish are disoriented, their movements uncoordinated, their breathing rapid, gills swollen, and they have local skin lesions. The virus was isolated from tissue of diseased fish and cultivated on a KF-1 (koi fin cells cell line. Electronic microscopy examinations revealed virus identical viral particles of the Herpesviridae family. Analyses of the virion polypeptide and DNA established differences between the KHV and the previously known herpesvirus of the Cyprinida family, Herpesvirus cyprini (CHV, and the virus of the channel catfish (Channel catfish virus - CCV. In the years 2004 and 2005, high mortality was established among one-year and two-year carp fry on three fish ponds. At two ponds, the deaths occurred among one year and two

  13. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

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    Peremot S. D

    2016-12-01

    Full Text Available Viral myocarditis is a heterogeneous group of diseases not only by etiologic factors, which belong to different families of Vira kingdom, but is also characterized by a unique mechanism of inflammatory process and cytokine levels specific for each of them. According to numerous researches in сardio-immunology, at herpesvirus infection of the cardiovascular system occur both systemic and localized violations of the immune response. Unfortunately, the accessible literature did not provide the data analysis of complex cardio-immunological research that would take into account the features of herpesvirus myocarditis clinical course. This grounds relevance of immunodiagnosis directed on the exposure of dysimmunities by study of indices of general and local immunity with the estimation of the immune status in patients depending on the stage of exasperation or relapse of chronic herpetic infection in the complex of diagnostic tests. The purpose of our research was to determine features of the state of the immune system with the complex analysis of cytokine profile data, immune and interferon statuses in subacute and chronic forms of herpesvirus myocarditis. Materials and methods. 87 myocarditis patients who were receiving inpatient treatment in medical establishments of Kharkiv were examined. The average age was (M ± m 36 ± 3,46 years old. The diagnosis of myocarditis was established according to the order № 436 by the Ministry of Healthcare of Ukraine from 03.07.2006 of clinical findings protocol. In accordance with the term of myocarditis clinical course, the patients were divided in two sub-groups: 44 patients with subacute (from 2 to 6 months, and 43 patients with chronic (over 6 months clinical course of viral myocarditis. The control group correlated with patients of basic group by age and gender and consisted of 40 practically healthy persons without implications of cardial pathology. Definition of cytokine concentration: IL-2, IL-4, IL-6

  14. Targeting herpesvirus reliance of the chemokine system

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N

    2006-01-01

    the infection. However, since both virus and host exist, the organisms struggle must reach an ecological equilibrium. Among the best-studied interactions between viruses and the host immune system are those between herpesviruses and their hosts. Herpesviruses are known to devote a significant part...... of their large genomes on immuno-modulatory genes, some encoding chemokines or chemokine receptors. These genes, which may be dispensable for viral replication in vitro, are highly important for viral growth in vivo, for viral dissemination and disease progression. Indeed, all beta and gamma-herpesviruses have...... chemokine receptors seems to be their constitutive activity. The biological function of the constitutive activity is still unclear, but it has become clear that the receptors are involved in important parts of the viral lifecycle in vivo, and that the receptor signaling is involved in gamma-herpesvirus...

  15. [Research Advances in Cyprinid Herpesvirus 3].

    Science.gov (United States)

    Zheng, Shucheng; Wang, Qing; Li, Yingying; Zeng, Weiwei; Wang, Yingying; Liu, Chun; Liang, Hongru; Shi, Cunbin

    2016-01-01

    Cyprinid herpesvirus 3 (CyHV-3) is the causative agent of an extremely contagious and aggressive disease afflicting common corp Cyprinus carpio L. termed koi herpesvirus disease (KHVD). Since it was first reported in 1997, the virus has spread worldwide rapidly, leading to enormous financial losses in industries based on common carp and koi carp. This review summarizes recent advances in CyHV-3 research on the etiology, epidemiology, pathogenesis, diagnosis, prevention, and control of KHVD.

  16. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.

    Science.gov (United States)

    Tzannou, Ifigeneia; Papadopoulou, Anastasia; Naik, Swati; Leung, Kathryn; Martinez, Caridad A; Ramos, Carlos A; Carrum, George; Sasa, Ghadir; Lulla, Premal; Watanabe, Ayumi; Kuvalekar, Manik; Gee, Adrian P; Wu, Meng-Fen; Liu, Hao; Grilley, Bambi J; Krance, Robert A; Gottschalk, Stephen; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Leen, Ann M; Omer, Bilal

    2017-11-01

    Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.

  17. Persistence of herpesvirus of eel (Herpesvirus anguillae) in farmed European ell (Anguilla anguilla L.)

    NARCIS (Netherlands)

    Nieuwstadt, van A.P.; Dijkstra, S.G.; Haenen, O.L.M.

    2001-01-01

    Herpesvirus of eel Herpesvirus anguillae (HVA) was isolated repeatedly from farmed eel of an outwardly healthy stock, but virus isolation was much greater in an experimental group of fish that were injected with dexamethasone. The results suggest that HVA can establish a latent infection in eel.

  18. Lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats: a systematic review.

    Science.gov (United States)

    Bol, Sebastiaan; Bunnik, Evelien M

    2015-11-16

    Feline herpesvirus 1 is a highly contagious virus that affects many cats. Virus infection presents with flu-like signs and irritation of ocular and nasal regions. While cats can recover from active infections without medical treatment, examination by a veterinarian is recommended. Lysine supplementation appears to be a popular intervention (recommended by > 90 % of veterinarians in cat hospitals). We investigated the scientific merit of lysine supplementation by systematically reviewing all relevant literature. NCBI's PubMed database was used to search for published work on lysine and feline herpesvirus 1, as well as lysine and human herpesvirus 1. Seven studies on lysine and feline herpesvirus 1 (two in vitro studies and 5 studies with cats), and 10 publications on lysine and human herpesvirus 1 (three in vitro studies and 7 clinical trials) were included for qualitative analysis. There is evidence at multiple levels that lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats. Lysine does not have any antiviral properties, but is believed to act by lowering arginine levels. However, lysine does not antagonize arginine in cats, and evidence that low intracellular arginine concentrations would inhibit viral replication is lacking. Furthermore, lowering arginine levels is highly undesirable since cats cannot synthesize this amino acid themselves. Arginine deficiency will result in hyperammonemia, which may be fatal. In vitro studies with feline herpesvirus 1 showed that lysine has no effect on the replication kinetics of the virus. Finally, and most importantly, several clinical studies with cats have shown that lysine is not effective for the prevention or the treatment of feline herpesvirus 1 infection, and some even reported increased infection frequency and disease severity in cats receiving lysine supplementation. We recommend an immediate stop of lysine supplementation because of the complete lack of

  19. Characterization of phocid herpesvirus-1 and -2 as putative alpha- and gamma-herpesviruses of North American and European pinnipeds.

    NARCIS (Netherlands)

    T.C. Harder (Timm); M. Harder; H. Vos; K. Kulonen; S. Kennedy-Stoskopf; B. Liess; M.J.G. Appel (Max); A.D.M.E. Osterhaus (Albert)

    1996-01-01

    textabstractTo study the relationships between herpesvirus recently isolated from different pinniped species, antigenic and genetic analyses were performed. First, herpesviruses isolated from North American harbour seals (Phoca vitulina), a Californian sea lion (Zalophus californianus) and a

  20. Altered GPM6A/M6 Dosage Impairs Cognition and Causes Phenotypes Responsive to Cholesterol in Human and Drosophila

    NARCIS (Netherlands)

    Gregor, A.; Kramer, J.M.; Voet, M. van der; Schanze, I.; Uebe, S.; Donders, R.; Reis, A.; Schenck, A.; Zweier, C.

    2014-01-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral

  1. Favourable effect of chemotherapy on clinical symptoms and human herpesvirus-8 DNA load in a patient with Kaposi's sarcoma presenting with fever and anemia

    NARCIS (Netherlands)

    Prins, J. M.; Sol, C. J.; Renwick, N.; Goudsmit, J.; Veenstra, J.; Reiss, P.

    1999-01-01

    The case of a patient infected with human immunodeficiency virus type 1 (HIV-1) with Kaposi's sarcoma who presented with fever of unknown origin, severe anemia, thrombocytopenia and hypoalbuminemia but only limited involvement of the skin is presented. Chemotherapy directed at Kaposi's sarcoma

  2. Koi herpesvirus represents a third cyprinid herpesvirus (CyHV-3) in the family Herpesviridae.

    Science.gov (United States)

    Waltzek, Thomas B; Kelley, Garry O; Stone, David M; Way, Keith; Hanson, Larry; Fukuda, Hideo; Hirono, Ikuo; Aoki, Takashi; Davison, Andrew J; Hedrick, Ronald P

    2005-06-01

    The sequences of four complete genes were analysed in order to determine the relatedness of koi herpesvirus (KHV) to three fish viruses in the family Herpesviridae: carp pox herpesvirus (Cyprinid herpesvirus 1, CyHV-1), haematopoietic necrosis herpesvirus of goldfish (Cyprinid herpesvirus 2, CyHV-2) and channel catfish virus (Ictalurid herpesvirus 1, IcHV-1). The genes were predicted to encode a helicase, an intercapsomeric triplex protein, the DNA polymerase and the major capsid protein. The results showed that KHV is related closely to CyHV-1 and CyHV-2, and that the three cyprinid viruses are related, albeit more distantly, to IcHV-1. Twelve KHV isolates from four diverse geographical areas yielded identical sequences for a region of the DNA polymerase gene. These findings, with previously published morphological and biological data, indicate that KHV should join the group of related lower-vertebrate viruses in the family Herpesviridae under the formal designation Cyprinid herpesvirus 3 (CyHV-3).

  3. Known regulators of nitric oxide synthase and arginase are agonists at the human G-protein-coupled receptor GPRC6A

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Wellendorph, Petrine; Bräuner-Osborne, Hans

    2006-01-01

    receptor construct, h6A/5.24, containing the ligand-binding amino-terminal domain of the human GPRC6A and the seven-transmembrane domain and carboxy terminus of the homologous goldfish receptor 5.24. Based on knowledge that this chimera prefers basic L-alpha-amino acids such as arginine, lysine...

  4. Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

    Science.gov (United States)

    Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

    2017-09-24

    We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

  5. Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India

    Directory of Open Access Journals (Sweden)

    Vijay P Bondre

    2016-01-01

    Interpretation & conclusions: Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections.

  6. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

    Science.gov (United States)

    Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

    2014-12-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. © 2014 WILEY PERIODICALS, INC.

  7. Koi herpesvirus disease (khvd) surveillance and diagnosis

    DEFF Research Database (Denmark)

    Way, K.; Bergmann, S. M.; Engelsma, Marc

    together skills and experience on this fish disease from different parts of Europe. In the report of the meeting sent to the commission important issues concerning serology and cyprinid herpesvirus variants were raised. We hope that our recommendations to resolve these issues will be considered...

  8. Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74

    DEFF Research Database (Denmark)

    McLean, Katherine A; Holst, Peter J; Martini, Lene

    2004-01-01

    The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74 from human herpesvirus 8 are both constitutively active. We show that both receptors constitutively activate the transcription factors nuclear factor of activated T cells (NFAT) and cAMP response element binding...

  9. An Epstein–Barr-related herpesvirus from marmoset lymphomas

    Science.gov (United States)

    Cho, Young-Gyu; Ramer, Jan; Rivailler, Pierre; Quink, Carol; Garber, Richard L.; Beier, David R.; Wang, Fred

    2001-01-01

    Epstein–Barr virus (EBV) is implicated in the development of human B cell lymphomas and carcinomas. Although related oncogenic herpesviruses were believed to be endemic only in Old World primate species, we now find these viruses to be endemic in New World primates. We have isolated a transforming, EBV-related virus from spontaneous B cell lymphomas of common marmosets (Callithrix jacchus). Sequencing of two-thirds of the genome reveals considerable divergence from the genomes of EBV and Old World primate EBV-related viruses, including differences in genes important for virus-induced cell growth transformation and pathogenesis. DNA related to the C. jacchus herpesvirus is frequently detected in squirrel monkey peripheral blood lymphocytes, indicating that persistent infection with EBV-related viruses is prevalent in both New World primate families. Understanding how these more divergent EBV-related viruses achieve similar biologic outcomes in their natural host is likely to provide important insights into EBV infection, B cell growth transformation, and oncogenesis. PMID:11158621

  10. Proteomic characterization of murid herpesvirus 4 extracellular virions.

    Directory of Open Access Journals (Sweden)

    Sarah Vidick

    Full Text Available Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV and the Kaposi's sarcoma associated herpesvirus (KSHV are highly prevalent pathogens that have been associated with several neoplastic diseases. As EBV and KSHV are host-range specific and replicate poorly in vitro, animal counterparts such as Murid herpesvirus-4 (MuHV-4 have been widely used as models. In this study, we used MuHV-4 in order to improve the knowledge about proteins that compose gammaherpesviruses virions. To this end, MuHV-4 extracellular virions were isolated and structural proteins were identified using liquid chromatography tandem mass spectrometry-based proteomic approaches. These analyses allowed the identification of 31 structural proteins encoded by the MuHV-4 genome which were classified as capsid (8, envelope (9, tegument (13 and unclassified (1 structural proteins. In addition, we estimated the relative abundance of the identified proteins in MuHV-4 virions by using exponentially modified protein abundance index analyses. In parallel, several host proteins were found in purified MuHV-4 virions including Annexin A2. Although Annexin A2 has previously been detected in different virions from various families, its role in the virion remains controversial. Interestingly, despite its relatively high abundance in virions, Annexin A2 was not essential for the growth of MuHV-4 in vitro. Altogether, these results extend previous work aimed at determining the composition of gammaherpesvirus virions and provide novel insights for understanding MuHV-4 biology.

  11. Sequencing of bovine herpesvirus 4 v.test strain reveals important genome features

    Directory of Open Access Journals (Sweden)

    Gillet Laurent

    2011-08-01

    Full Text Available Abstract Background Bovine herpesvirus 4 (BoHV-4 is a useful model for the human pathogenic gammaherpesviruses Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus. Although genome manipulations of this virus have been greatly facilitated by the cloning of the BoHV-4 V.test strain as a Bacterial Artificial Chromosome (BAC, the lack of a complete genome sequence for this strain limits its experimental use. Methods In this study, we have determined the complete sequence of BoHV-4 V.test strain by a pyrosequencing approach. Results The long unique coding region (LUR consists of 108,241 bp encoding at least 79 open reading frames and is flanked by several polyrepetitive DNA units (prDNA. As previously suggested, we showed that the prDNA unit located at the left prDNA-LUR junction (prDNA-G differs from the other prDNA units (prDNA-inner. Namely, the prDNA-G unit lacks the conserved pac-2 cleavage and packaging signal in its right terminal region. Based on the mechanisms of cleavage and packaging of herpesvirus genomes, this feature implies that only genomes bearing left and right end prDNA units are encapsulated into virions. Conclusions In this study, we have determined the complete genome sequence of the BAC-cloned BoHV-4 V.test strain and identified genome organization features that could be important in other herpesviruses.

  12. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

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    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  13. Equid herpesvirus type 1 activates platelets.

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    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  14. Single tube multiplex real-time PCR for the rapid detection of herpesvirus infections of the central nervous system.

    Science.gov (United States)

    Sankuntaw, Nipaporn; Sukprasert, Saovaluk; Engchanil, Chulapan; Kaewkes, Wanlop; Chantratita, Wasun; Pairoj, Vantanit; Lulitanond, Viraphong

    2011-01-01

    Human herpesvirus infection of immunocompromised hosts may lead to central nervous system (CNS) infection and diseases. In this study, a single tube multiplex real-time PCR was developed for the detection of five herpesviruses (HSV-1, HSV-2, VZV, EBV and CMV) in clinical cerebrospinal fluid (CSF) specimens. Two primer pairs specific for the herpesvirus polymerase gene and five hybridization probe pairs for the specific identification of the herpesvirus types were used in a LightCycler multiplex real-time PCR. A singleplex real-time PCR was first optimized and then applied to the multiplex real-time PCR. The singleplex and multiplex real-time PCRs showed no cross-reactivity. The sensitivity of the singleplex real-time PCR was 1 copy per reaction for each herpesvirus, while that of the multiplex real-time PCR was 1 copy per reaction for HSV-1 and VZV and 10 copies per reaction for HSV-2, EBV and CMV. Intra and inter-assay variations of the single tube multiplex assay were in the range of 0.02%-3.67% and 0.79%-4.35%, respectively. The assay was evaluated by testing 62 clinical CSF samples and was found to have equivalent sensitivity, specificity and agreement as the routine real-time PCR, but reducing time, cost and amount of used sample. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Three novel herpesviruses of endangered Clemmys and Glyptemys turtles.

    Science.gov (United States)

    Ossiboff, Robert J; Raphael, Bonnie L; Ammazzalorso, Alyssa D; Seimon, Tracie A; Newton, Alisa L; Chang, Tylis Y; Zarate, Brian; Whitlock, Alison L; McAloose, Denise

    2015-01-01

    The rich diversity of the world's reptiles is at risk due to significant population declines of broad taxonomic and geographic scope. Significant factors attributed to these declines include habitat loss, pollution, unsustainable collection and infectious disease. To investigate the presence and significance of a potential pathogen on populations of critically endangered bog turtles (Glyptemys muhlenbergii) as well sympatric endangered wood (G. insculpta) and endangered spotted (Clemmys guttata) turtles in the northeastern United States, choanal and cloacal swabs collected from 230 turtles from 19 sites in 5 states were screened for herpesvirus by polymerase chain reaction. We found a high incidence of herpesvirus infection in bog turtles (51.5%; 105/204) and smaller numbers of positive wood (5) and spotted (1) turtles. Sequence and phylogenetic analysis revealed three previously uncharacterized alphaherpesviruses. Glyptemys herpesvirus 1 was the predominant herpesvirus detected and was found exclusively in bog turtles in all states sampled. Glyptemys herpesvirus 2 was found only in wood turtles. Emydid herpesvirus 2 was found in a small number of bog turtles and a single spotted turtle from one state. Based on these findings, Glyptemys herpesvirus 1 appears to be a common infection in the study population, whereas Glyptemys herpesvirus 2 and Emydid herpesvirus 2 were not as frequently detected. Emydid herpesvirus 2 was the only virus detected in more than one species. Herpesviruses are most often associated with subclinical or mild infections in their natural hosts, and no sampled turtles showed overt signs of disease at sampling. However, infection of host-adapted viruses in closely related species can result in significant disease. The pathogenic potential of these viruses, particularly Emydid herpesvirus 2, in sympatric chelonians warrants additional study in order to better understand the relationship of these viruses with their endangered hosts.

  16. The role of DNA repair in herpesvirus pathogenesis.

    Science.gov (United States)

    Brown, Jay C

    2014-10-01

    In cells latently infected with a herpesvirus, the viral DNA is present in the cell nucleus, but it is not extensively replicated or transcribed. In this suppressed state the virus DNA is vulnerable to mutagenic events that affect the host cell and have the potential to destroy the virus' genetic integrity. Despite the potential for genetic damage, however, herpesvirus sequences are well conserved after reactivation from latency. To account for this apparent paradox, I have tested the idea that host cell-encoded mechanisms of DNA repair are able to control genetic damage to latent herpesviruses. Studies were focused on homologous recombination-dependent DNA repair (HR). Methods of DNA sequence analysis were employed to scan herpesvirus genomes for DNA features able to activate HR. Analyses were carried out with a total of 39 herpesvirus DNA sequences, a group that included viruses from the alpha-, beta- and gamma-subfamilies. The results showed that all 39 genome sequences were enriched in two or more of the eight recombination-initiating features examined. The results were interpreted to indicate that HR can stabilize latent herpesvirus genomes. The results also showed, unexpectedly, that repair-initiating DNA features differed in alpha- compared to gamma-herpesviruses. Whereas inverted and tandem repeats predominated in alpha-herpesviruses, gamma-herpesviruses were enriched in short, GC-rich initiation sequences such as CCCAG and depleted in repeats. In alpha-herpesviruses, repair-initiating repeat sequences were found to be concentrated in a specific region (the S segment) of the genome while repair-initiating short sequences were distributed more uniformly in gamma-herpesviruses. The results suggest that repair pathways are activated differently in alpha- compared to gamma-herpesviruses. Copyright © 2014. Published by Elsevier Inc.

  17. Three Novel Herpesviruses of Endangered Clemmys and Glyptemys Turtles

    Science.gov (United States)

    Ossiboff, Robert J.; Raphael, Bonnie L.; Ammazzalorso, Alyssa D.; Seimon, Tracie A.; Newton, Alisa L.; Chang, Tylis Y.; Zarate, Brian; Whitlock, Alison L.; McAloose, Denise

    2015-01-01

    The rich diversity of the world’s reptiles is at risk due to significant population declines of broad taxonomic and geographic scope. Significant factors attributed to these declines include habitat loss, pollution, unsustainable collection and infectious disease. To investigate the presence and significance of a potential pathogen on populations of critically endangered bog turtles (Glyptemys muhlenbergii) as well sympatric endangered wood (G. insculpta) and endangered spotted (Clemmys guttata) turtles in the northeastern United States, choanal and cloacal swabs collected from 230 turtles from 19 sites in 5 states were screened for herpesvirus by polymerase chain reaction. We found a high incidence of herpesvirus infection in bog turtles (51.5%; 105/204) and smaller numbers of positive wood (5) and spotted (1) turtles. Sequence and phylogenetic analysis revealed three previously uncharacterized alphaherpesviruses. Glyptemys herpesvirus 1 was the predominant herpesvirus detected and was found exclusively in bog turtles in all states sampled. Glyptemys herpesvirus 2 was found only in wood turtles. Emydid herpesvirus 2 was found in a small number of bog turtles and a single spotted turtle from one state. Based on these findings, Glyptemys herpesvirus 1 appears to be a common infection in the study population, whereas Glyptemys herpesvirus 2 and Emydid herpesvirus 2 were not as frequently detected. Emydid herpesvirus 2 was the only virus detected in more than one species. Herpesviruses are most often associated with subclinical or mild infections in their natural hosts, and no sampled turtles showed overt signs of disease at sampling. However, infection of host-adapted viruses in closely related species can result in significant disease. The pathogenic potential of these viruses, particularly Emydid herpesvirus 2, in sympatric chelonians warrants additional study in order to better understand the relationship of these viruses with their endangered hosts. PMID

  18. Three novel herpesviruses of endangered Clemmys and Glyptemys turtles.

    Directory of Open Access Journals (Sweden)

    Robert J Ossiboff

    Full Text Available The rich diversity of the world's reptiles is at risk due to significant population declines of broad taxonomic and geographic scope. Significant factors attributed to these declines include habitat loss, pollution, unsustainable collection and infectious disease. To investigate the presence and significance of a potential pathogen on populations of critically endangered bog turtles (Glyptemys muhlenbergii as well sympatric endangered wood (G. insculpta and endangered spotted (Clemmys guttata turtles in the northeastern United States, choanal and cloacal swabs collected from 230 turtles from 19 sites in 5 states were screened for herpesvirus by polymerase chain reaction. We found a high incidence of herpesvirus infection in bog turtles (51.5%; 105/204 and smaller numbers of positive wood (5 and spotted (1 turtles. Sequence and phylogenetic analysis revealed three previously uncharacterized alphaherpesviruses. Glyptemys herpesvirus 1 was the predominant herpesvirus detected and was found exclusively in bog turtles in all states sampled. Glyptemys herpesvirus 2 was found only in wood turtles. Emydid herpesvirus 2 was found in a small number of bog turtles and a single spotted turtle from one state. Based on these findings, Glyptemys herpesvirus 1 appears to be a common infection in the study population, whereas Glyptemys herpesvirus 2 and Emydid herpesvirus 2 were not as frequently detected. Emydid herpesvirus 2 was the only virus detected in more than one species. Herpesviruses are most often associated with subclinical or mild infections in their natural hosts, and no sampled turtles showed overt signs of disease at sampling. However, infection of host-adapted viruses in closely related species can result in significant disease. The pathogenic potential of these viruses, particularly Emydid herpesvirus 2, in sympatric chelonians warrants additional study in order to better understand the relationship of these viruses with their endangered hosts.

  19. Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function

    DEFF Research Database (Denmark)

    Jorgensen, Stine; Have, Christian Theil; Underwood, Christina Rye

    2017-01-01

    -expressed murine and goldfish orthologs. The latter orthologs are Gq-coupled and lead to intracellular accumulation of inositol phosphates and calcium release. In the present study we cloned the bonobo chimpanzee GPRC6A receptor, which is 99% identical to the human receptor, and show that it is cell surface...

  20. The complete genome sequence of herpesvirus papio 2 (Cercopithecine herpesvirus 16) shows evidence of recombination events among various progenitor herpesviruses.

    Science.gov (United States)

    Tyler, Shaun D; Severini, Alberto

    2006-02-01

    We have sequenced the entire genome of herpesvirus papio 2 (HVP-2; Cercopithecine herpesvirus 16) strain X313, a baboon herpesvirus with close homology to other primate alphaherpesviruses, such as SA8, monkey B virus, and herpes simplex virus (HSV) type 1 and type 2. The genome of HVP-2 is 156,487 bp in length, with an overall GC content of 76.5%. The genome organization is identical to that of the other members of the genus Simplexvirus, with a long and a short unique region, each bordered by inverted repeats which end with an "a" sequence. All of the open reading frames detected in this genome were homologous and colinear with those of SA8 and B virus. The HSV gene RL1 (gamma(1)34.5; neurovirulence factor) is not present in HVP-2, as is the case for SA8 and B virus. The HVP-2 genome is 85% homologous to its closest relative, SA8. However, segment-by-segment bootstrap analysis of the genome revealed at least two regions that display closer homology to the corresponding sequences of B virus. The first region comprises the UL41 to UL44 genes, and the second region is located within the UL36 gene. We hypothesize that this localized and defined shift in homology is due to recombination events between an SA8-like progenitor of HVP-2 and a herpesvirus species more closely related to the B virus. Since some of the genes involved in these putative recombination events are determinants of virulence, a comparative analysis of their function may provide insight into the pathogenic mechanism of simplexviruses.

  1. [Herpesvirus detection in clinically healthy West African mud turtles (Pelusioscastaneus)].

    Science.gov (United States)

    Marschang, R E; Heckers, K O; Heynol, V; Weider, K; Behncke, H

    2015-01-01

    First description of a herpesvirus in West African mud turtles. A herpesvirus was detected in two clinically healthy West African mud turtles (Pelusios castaneus) by PCR during a quarantine exam. The animals had been imported from Togo, West Africa to Germany for the pet trade. Analysis of a portion of the genome of the detected virus showed that it is a previously unknown virus related to other chelonid herpesviruses. The virus was named pelomedusid herpesvirus 1. This case highlights the importance of testing for infectious agents during quarantine, even in clinically healthy animals.

  2. Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.

    Science.gov (United States)

    Staheli, Jeannette P; Dyen, Michael R; Deutsch, Gail H; Basom, Ryan S; Fitzgibbon, Matthew P; Lewis, Patrick; Barcy, Serge

    2016-08-01

    Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally

  3. Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

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    Roberta Santarelli

    2015-01-01

    Full Text Available We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi’s sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to γ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis.

  4. Nuclear Exodus: Herpesviruses Lead the Way

    Science.gov (United States)

    Bigalke, Janna M.; Heldwein, Ekaterina E.

    2016-01-01

    Most DNA viruses replicate in the nucleus and exit it either by passing through the nuclear pores or by rupturing the nuclear envelope. Unusually, herpesviruses have evolved a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. Although this general scheme is accepted in the field, the players and their roles are still debated. Recent studies illuminated critical mechanistic features of this enigmatic process and uncovered surprising parallels with a novel cellular nuclear export process. This review summarizes our current understanding of nuclear egress in herpesviruses, examines the experimental evidence and models, and outlines outstanding questions with the goal of stimulating new research in this area. PMID:27482898

  5. Herpesvirus infections in psittacine birds in Japan.

    Science.gov (United States)

    Tsai, S S; Park, J H; Hirai, K; Itakura, C

    1993-03-01

    Herpesvirus infection was diagnosed histologically and electron microscopically in 21 out of 241 pet birds examined. The infected birds included 14 parakeets (Psittacula krameri manillensis) with respiratory infection and three parrots (Ama-zona aestiva aestiva), two cockatiels (Nymphicus hollandicus) and two rosellas (Platycercus emimius) with Pacheco's disease. The consistent lesions of respiratory herpesvirus infection were the formation of syncytial cells associated with the presence of intranuclear inclusion bodies, mainly in the lung and air sac. There was lack of an apparent cellular reaction in situ. The agent induced tubular structures containing a clear core in the nuclei of the affected cells. The present study indicated that it was a distinct entity from infectious laryngotracheitis based on tissue tropism, host reaction and morphology of the tubular structures. The striking lesions of Pacheco's disease consisted of syncytial cell formation with intranuclear inclusion bodies in various organs, especially the liver, parathyroid, ovary, bone marrow and intestine. This agent showed similar morphology to that of the respiratory herpesvirus infection, but was larger in size and had no tubular structure formation in the nuclei of affected cells.

  6. Immunofluorescent staining of nuclear antigen in lymphoid cells transformed by Herpesvirus papio (HVP).

    Science.gov (United States)

    Schmitz, H

    1981-01-01

    An improved fixation method for antigen detection in lymphoblastoid cells is described. Herpesvirus papio nuclear antigen (HUPNA) could be stained in several transformed lymphoid cell lines by anti-complement immunofluorescence (ACIF). Antibody to HUPNA was detected in many human sera containing antibodies to Epstein-Barr virus capsid and nuclear antigen (EBNA). Rheumatoid arthritis sera showed a high incidence of both anti-EBNA and anti-HUPNA antibodies.

  7. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

    1999-01-01

    A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...

  8. Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators Detecção imuno-histoquímica do antígeno nuclear latente-1 do herpesvirus tipo 8 para diferenciar o sarcoma de Kaposi epidêmico cutâneo de seus simuladores histológicos

    Directory of Open Access Journals (Sweden)

    Patricia Fonseca Pereira

    2013-04-01

    Full Text Available Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8 latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.O sarcoma de Kaposi é a neoplasia mais diagnosticada em pacientes com SIDA e a expressão do antígeno nuclear latente-1 do herpesvírus humano tipo-8 (HHV-8 tem se mostrado útil no seu diagnóstico histológico. O objetivo deste estudo é confirmar que o método imuno-histoquímico é uma ferramenta útil para diferenciar o sarcoma de Kaposi cutâneo de seus simuladores histológicos em pacientes HIV positivos. Análise histológica e imuno-histoquímica foram realizadas em 49 casos de sarcoma de Kaposi cutâneo e 60 casos de seus simuladores histológicos. Positividade à imuno-histoquímica para o antígeno nuclear latente 1 do HHV-8 foi observada nos 49 casos de sarcoma de Kaposi e nenhuma reação foi detectada nos 60 simuladores analisados, resultando em 100% de sensibilidade e especificidade. A detecção do HHV-8 por imuno-histoquímica é uma ferramenta útil para o diagnóstico de sarcoma de Kaposi, especialmente na lesão inicial cujo caráter neoplásico não é evidente, e contribui para seu diagnóstico diferencial histológico.

  9. Absence of frequent herpesvirus transmission in a nonhuman primate predator-prey system in the wild.

    Science.gov (United States)

    Murthy, Sripriya; Couacy-Hymann, Emmanuel; Metzger, Sonja; Nowak, Kathrin; De Nys, Helene; Boesch, Christophe; Wittig, Roman; Jarvis, Michael A; Leendertz, Fabian H; Ehlers, Bernhard

    2013-10-01

    Emergence of viruses into the human population by transmission from nonhuman primates (NHPs) represents a serious potential threat to human health that is primarily associated with the increased bushmeat trade. Transmission of RNA viruses across primate species appears to be relatively frequent. In contrast, DNA viruses appear to be largely host specific, suggesting low transmission potential. Herein, we use a primate predator-prey system to study the risk of herpesvirus transmission between different primate species in the wild. The system was comprised of western chimpanzees (Pan troglodytes verus) and their primary (western red colobus, Piliocolobus badius badius) and secondary (black-and-white colobus, Colobus polykomos) prey monkey species. NHP species were frequently observed to be coinfected with multiple beta- and gammaherpesviruses (including new cytomegalo- and rhadinoviruses). However, despite frequent exposure of chimpanzees to blood, organs, and bones of their herpesvirus-infected monkey prey, there was no evidence for cross-species herpesvirus transmission. These findings suggest that interspecies transmission of NHP beta- and gammaherpesviruses is, at most, a rare event in the wild.

  10. Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44high CD62Llow CD8+ TEM Cells and Protect Humanized HLA-A*02:01 Transgenic Mice against Ocular Herpesvirus Infection.

    Science.gov (United States)

    Srivastava, Ruchi; Khan, Arif A; Garg, Sumit; Syed, Sabrina A; Furness, Julie N; Vahed, Hawa; Pham, Tiffany; Yu, Howard T; Nesburn, Anthony B; BenMohamed, Lbachir

    2017-01-15

    Herpes simplex virus 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8 + T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8 + T cells play a role in the natural protection seen in asymptomatic (ASYMP) individuals (individuals who have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8 + T-cell epitopes from the 693-amino-acid sequence of the VP13/14 protein. Three out of 10 epitopes exhibited a high to moderate affinity of binding to soluble HLA-A*02:01 molecules. The phenotype and function of CD8 + T cells specific for each epitope were compared in HLA-A*02:01-positive ASYMP individuals and symptomatic (SYMP) individuals (individuals who have frequent clinical herpetic diseases) using determination of a combination of tetramer frequency and the levels of granzyme B, granzyme K, perforin, gamma interferon, tumor necrosis factor alpha, and interleukin-2 production and CD107 a/b cytotoxic degranulation. High frequencies of multifunctional CD8 + T cells directed against three epitopes, VP13/14 from amino acids 286 to 294 (VP13/14 286-294 ), VP13/14 from amino acids 504 to 512 (VP13/14 504-512 ), and VP13/14 from amino acids 544 to 552 (VP13/14 544-552 ), were detected in ASYMP individuals, while only low frequencies were detected in SYMP individuals. The three epitopes also predominantly recalled more CD45RA low CD44 high CCR7 low CD62L low CD8 + effector memory T cells (T EM cells) in ASYMP individuals than SYMP individuals. Moreover, immunization of HLA-A*02:01 transgenic mice with the three CD8 + T EM -cell epitopes from ASYMP individuals induced robust and polyfunctional HSV-specific CD8 + T EM cells associated with strong protective immunity against ocular herpesvirus infection and disease. Our findings outline the phenotypic

  11. Age-Related Macular Degeneration: A Connection between Human Herpes Virus-6A-Induced CD46 Downregulation and Complement Activation?

    Directory of Open Access Journals (Sweden)

    Walter Fierz

    2017-10-01

    Full Text Available Viruses are able to interfere with the immune system by docking to receptors on host cells that are important for proper functioning of the immune system. A well-known example is the human immunodeficiency virus that uses CD4 cell surface molecules to enter host lymphocytes and thereby deleteriously destroying the helper cell population of the immune system. A more complicated mechanism is seen in multiple sclerosis (MS where human herpes virus-6A (HHV-6A infects astrocytes by docking to the CD46 surface receptor. Such HHV-6A infection in the brain of MS patients has recently been postulated to enable Epstein–Barr virus (EBV to transform latently infected B-lymphocytes in brain lesions leading to the well-known phenomenon of oligoclonal immunoglobulin production that is widely used in the diagnosis of MS. The cellular immune response to HHV-6A and EBV is one part of the pathogenic mechanisms in MS. A more subtle pathogenic mechanism can be seen in the downregulation of CD46 on astrocytes by the infecting HHV-6A. Since CD46 is central in regulating the complement system, a lack of CD46 can lead to hyperactivation of the complement system. In fact, activation of the complement system in brain lesions is a well-known pathogenic mechanism in MS. In this review, it is postulated that a similar mechanism is central in the development of age-related macular degeneration (AMD. One of the earliest changes in the retina of AMD patients is the loss of CD46 expression in the retinal pigment epithelial (RPE cells in the course of geographic atrophy. Furthermore, CD46 deficient mice spontaneously develop dry-type AMD-like changes in their retina. It is also well known that certain genetic polymorphisms in the complement-inhibiting pathways correlate with higher risks of AMD development. The tenet is that HHV-6A infection of the retina leads to downregulation of CD46 and consequently to hyperactivation of the complement system in the eyes of susceptible

  12. Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression.

    Directory of Open Access Journals (Sweden)

    Dongsha Wang

    Full Text Available The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET measures of brain serotonin (5-HT synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC. Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25 who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20 where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function.

  13. Putative periodontopathic bacteria and herpesviruses in pregnant women: a case-control study.

    Science.gov (United States)

    Lu, Haixia; Zhu, Ce; Li, Fei; Xu, Wei; Tao, Danying; Feng, Xiping

    2016-06-15

    Little is known about herpesvirus and putative periodontopathic bacteria in maternal chronic periodontitis. The present case-control study aimed to explore the potential relationship between putative periodontopathic bacteria and herpesviruses in maternal chronic periodontitis.Saliva samples were collected from 36 pregnant women with chronic periodontitis (cases) and 36 pregnant women with healthy periodontal status (controls). Six putative periodontopathic bacteria (Porphyromonas gingivalis [Pg], Aggregatibacer actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Prevotella intermedia [Pi], Tannerella forsythia [Tf], and Treponema denticola [Td]) and three herpesviruses (Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], and herpes simplex virus [HSV]) were detected. Socio-demographic data and oral health related behaviors, and salivary estradiol and progesterone levels were also collected. The results showed no significant differences in socio-demographic background, oral health related behaviors, and salivary estradiol and progesterone levels between the two groups (all P > 0.05). The detection rates of included periodontopathic microorganisms were not significantly different between the two groups (all P > 0.05), but the coinfection rate of EBV and Pg was significantly higher in the case group than in the control group (P = 0.028). EBV and Pg coinfection may promote the development of chronic periodontitis among pregnant women.

  14. [Molecular tests in diagnosis of Cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) using real-time PCR in HIV positive and HIV-negative pregnant women in Ouagadougou, Burkina Faso].

    Science.gov (United States)

    Ouedraogo, Alice Rogomenoma; Kabre, Madeleine; Bisseye, Cyrille; Zohoncon, Théodora Mahoukèdè; Asshi, Maleki; Soubeiga, Serge Théophile; Diarra, Birama; Traore, Lassina; Djigma, Florencia Wendkuuni; Ouermi, Djénéba; Pietra, Virginio; Barro, Nicolas; Simpore, Jacques

    2016-01-01

    Herpesvirus EBV, CMV and HHV-6 are viruses that evolve based on pandemic modeling and are responsible for congenital infections causing severe sequelae in infants. This study aims to determine the prevalence of CMV, EBV and HHV-6 among HIV (+) and HIV (-) pregnant women in Ouagadougou. In this study 200 blood plasma samples taken from pregnant women, of whom 100 with HIV(+) and 100 with HIV(-), were analyzed using multiplex real-time PCR which detected three infections (EBV, CMV and HHV-6). Out of the 200 samples tested, 18(9.0%) were positive for at least one of the three viruses, 12(6.0%) were positive for EBV, 13(6.5%) were positive for CMV and 12(6.0%) were positive for HHV-6. Among the 18 cases with infections, 10 cases (55.6%) had co-infections of whom 90.0% (9/10) with multiple EBV/CMV/HHV6 infection and 10.0% with EBV/HHV6 co-infection. HHVs infection rate was higher among HIV (-) pregnant women than among HIV (+) pregnant women (12.0% versus 6.0%). Among HIV (+) pregnant women, PCR showed 7.1% (6/85) of HHVs infection in patients who were not treated with ARV against 0% in those treated with ARVs. Herpes virus infections are a common condition in pregnant women in Burkina Faso. They may represent a real threat to pregnant women because of complications and risks of infection in infants.

  15. Polarized DNA Ejection from the Herpesvirus Capsid

    Science.gov (United States)

    Newcomb, William W.; Cockrell, Shelley K.; Homa, Fred L.; Brown, Jay C.

    2009-01-01

    Ejection of DNA from the capsid is an early step in infection by all herpesviruses. Ejection or DNA uncoating occurs after a parental capsid has entered the host cell cytoplasm, migrated to the nucleus and bound to a nuclear pore. DNA exits the capsid through the portal vertex and proceeds by way of the nuclear pore complex into the nucleoplasm where it is transcribed and replicated. Here we describe use of an in vitro uncoating system to determine which genome end exits first from the herpes simplex virus (HSV-1) capsid. Purified DNA-containing capsids were bound to a solid surface and warmed under conditions in which some, but not all, of the DNA was ejected. Restriction endonuclease digestion was then used to identify the genomic origin of the ejected DNA. The results support the view that the S segment end exits the capsid first. Preferential release at the S end demonstrates that herpesvirus DNA uncoating conforms to the paradigm in dsDNA bacteriophage where the last end packaged is the first to be ejected. Release of HSV-1 DNA beginning at the S end causes the first gene to enter the host cell nucleus to be α4, a transcription factor required for expression of early genes. PMID:19631662

  16. Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

    International Nuclear Information System (INIS)

    Kaleeba, Johnan A.R.; Berger, Edward A.

    2006-01-01

    The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of α3β1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor

  17. Isolation and characterization of a herpesvirus from feral pigeons in China.

    Science.gov (United States)

    Zhao, Panpan; Ma, Jian; Guo, Ying; Tian, Li; Guo, Guangyang; Zhang, Kexin; Xing, Mingwei

    2015-12-01

    A herpesvirus was isolated during a diagnostic investigation of severe cases of conjunctivitis in feral pigeons (Columba livia f. domestica). Isolates of the virus were recovered from throat swabs of the pigeons followed by inoculation of the swab samples in chicken embryo fibroblasts. Pigeons inoculated with the isolated virus had similar clinical signs to those observed in naturally infected birds. Transmission electron microscopy revealed viral structures with typical herpesvirus morphology. Polymerase chain reaction amplification, using herpesvirus-identifying primers resulted in an amplicon of the expected size for herpesvirus. Sequencing of these amplicons and database comparisons identified the herpesvirus UL30 homologue. Phylogenetic reconstructions suggested that the isolated herpesvirus belongs to the Mardivirus genus of Alphaherpesvirinae. Using the current herpesvirus nomenclature conventions, the authors propose that the herpesvirus be named Columbid herpesvirus-1 Heilongjiang. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

    Science.gov (United States)

    Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

    2003-05-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.

  19. The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome.

    Science.gov (United States)

    Ishida, T; Kano, Y; Mizukawa, Y; Shiohara, T

    2014-06-01

    Drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/TEN and beyond the acute stage of both diseases. Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS (n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV) DNA loads sequentially determined by real-time polymerase chain reaction during a 2-year period after onset. Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV-6 loads were exclusively detected in DIHS/DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them. Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow-up period, which may contribute, at least in part, to the difference in the clinical manifestations and long-term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/DRESS. © 2014 The Authors. Allergy Published by John Wiley & Sons Ltd.

  20. The First Endogenous Herpesvirus, Identified in the Tarsier Genome, and Novel Sequences from Primate Rhadinoviruses and Lymphocryptoviruses

    Science.gov (United States)

    Aswad, Amr; Katzourakis, Aris

    2014-01-01

    Herpesviridae is a diverse family of large and complex pathogens whose genomes are extremely difficult to sequence. This is particularly true for clinical samples, and if the virus, host, or both genomes are being sequenced for the first time. Although herpesviruses are known to occasionally integrate in host genomes, and can also be inherited in a Mendelian fashion, they are notably absent from the genomic fossil record comprised of endogenous viral elements (EVEs). Here, we combine paleovirological and metagenomic approaches to both explore the constituent viral diversity of mammalian genomes and search for endogenous herpesviruses. We describe the first endogenous herpesvirus from the genome of the Philippine tarsier, belonging to the Roseolovirus genus, and characterize its highly defective genome that is integrated and flanked by unambiguous host DNA. From a draft assembly of the aye-aye genome, we use bioinformatic tools to reveal over 100,000 bp of a novel rhadinovirus that is the first lemur gammaherpesvirus, closely related to Kaposi's sarcoma-associated virus. We also identify 58 genes of Pan paniscus lymphocryptovirus 1, the bonobo equivalent of human Epstein-Barr virus. For each of the viruses, we postulate gene function via comparative analysis to known viral relatives. Most notably, the evidence from gene content and phylogenetics suggests that the aye-aye sequences represent the most basal known rhadinovirus, and indicates that tumorigenic herpesviruses have been infecting primates since their emergence in the late Cretaceous. Overall, these data show that a genomic fossil record of herpesviruses exists despite their extremely large genomes, and expands the known diversity of Herpesviridae, which will aid the characterization of pathogenesis. Our analytical approach illustrates the benefit of intersecting evolutionary approaches with metagenomics, genetics and paleovirology. PMID:24945689

  1. Fluorescent Protein Approaches in Alpha Herpesvirus Research

    Directory of Open Access Journals (Sweden)

    Ian B. Hogue

    2015-11-01

    Full Text Available In the nearly two decades since the popularization of green fluorescent protein (GFP, fluorescent protein-based methodologies have revolutionized molecular and cell biology, allowing us to literally see biological processes as never before. Naturally, this revolution has extended to virology in general, and to the study of alpha herpesviruses in particular. In this review, we provide a compendium of reported fluorescent protein fusions to herpes simplex virus 1 (HSV-1 and pseudorabies virus (PRV structural proteins, discuss the underappreciated challenges of fluorescent protein-based approaches in the context of a replicating virus, and describe general strategies and best practices for creating new fluorescent fusions. We compare fluorescent protein methods to alternative approaches, and review two instructive examples of the caveats associated with fluorescent protein fusions, including describing several improved fluorescent capsid fusions in PRV. Finally, we present our future perspectives on the types of powerful experiments these tools now offer.

  2. Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies.

    Science.gov (United States)

    Zhu, Ce; Li, Fei; Wong, May Chun Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

    2015-01-01

    Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Ten eligible studies were included to investigate the association between Epstein-Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53-13.00, Pchronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41-9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95-8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21-4.86). The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV

  3. Herpesvirus capsid assembly and DNA packaging

    Science.gov (United States)

    Heming, Jason D.; Conway, James F.; Homa, Fred L.

    2017-01-01

    Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic infection. During productive lytic infection, over 80 viral proteins are expressed in a highly regulated manner, resulting in the replication of viral genomes and assembly of progeny virions. The virion of all herpesviruses consists of an external membrane envelope, a proteinaceous layer called the tegument, and an icosahedral capsid containing the double-stranded linear DNA genome. The capsid shell of HSV-1 is built from four structural proteins: a major capsid protein, VP5, which forms the capsomers (hexons and pentons), the triplex consisting of VP19C and VP23 found between the capsomers, and VP26 which binds to VP5 on hexons but not pentons. In addition, the dodecameric pUL6 portal complex occupies one of the 12 capsid vertices, and the capsid vertex specific component (CVSC), a heterotrimer complex of pUL17, pUL25 and pUL36 binds specifically to the triplexes adjacent to each penton. The capsid is assembled in the nucleus where the viral genome is packaged into newly assembled closed capsid shells. Cleavage and packaging of replicated, concatemeric viral DNA requires the seven viral proteins encoded by the UL6, UL15, UL17, UL25, UL28, UL32, and UL33 genes. Considerable advances have been made in understanding the structure of the herpesvirus capsid and the function of several of the DNA packaging proteins by applying biochemical, genetic, and structural techniques. This review is a summary of recent advances with respect to the structure of the HSV-1 virion capsid and what is known about the function of the seven packaging proteins and their interactions with each other and with the capsid shell. PMID:28528442

  4. Identification of a novel herpesvirus in captive Eastern box turtles (Terrapene carolina carolina).

    Science.gov (United States)

    Sim, Richard R; Norton, Terry M; Bronson, Ellen; Allender, Matthew C; Stedman, Nancy; Childress, April L; Wellehan, James F X

    2015-02-25

    Herpesviruses are significant pathogens of chelonians which most commonly cause upper respiratory tract disease and necrotizing stomatitis. Herpesvirus infection was identified in two populations of captive Eastern box turtles (Terrapene carolina carolina) using histopathology and polymerase chain reaction (PCR) with DNA sequencing. Necrotizing lesions with eosinophilic to amphophilic intranuclear inclusion bodies were identified in the tissues of one hatch-year individual in January 2013, which was herpesvirus positive by PCR. A separate captive group of adults had an observed herpesvirus prevalence of 58% using PCR in July 2011. In these cases, a novel herpesvirus, Terrapene herpesvirus 1 (TerHV1), was identified and serves as the first herpesvirus sequenced in the genus Terrapene. Similar to the other herpesviruses of the Order Testudines, TerHV1 clusters with the genus Scutavirus of the subfamily Alphaherpesvirinae. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Herpesvirus papio 2 encodes a virion host shutoff function.

    Science.gov (United States)

    Bigger, John E; Martin, David W

    2002-12-05

    Infection of baboons with herpesvirus papio 2 (HVP-2) produces a disease that is similar to human infection with herpes simplex viruses (HSV). Molecular characterization of HVP-2 has demonstrated that the virion contains a factor which rapidly shuts off host cell protein synthesis after infection. Reduction of host cell protein synthesis occurs in parallel with the degradation of mRNA species. A homolog of the HSV virion host shutoff (vhs) gene was identified by Southern and DNA sequence analysis. The sequence of the HVP-2 vhs gene homolog had greater than 70% identity with the vhs genes of HSV 1 and 2. Disruption of the HVP-2 vhs open reading frame diminished the ability of the virus to shut off protein synthesis and degrade cellular mRNA, indicating that this gene was responsible for the vhs activity. The HVP-2 model system provides the opportunity to study the biological role of vhs in the context of a natural primate host. Further development of this system will provide a platform for proof-of-concept studies that will test the efficacy of vaccines that utilize vhs-deficient viruses.

  6. Cyprinid Herpesvirus 3: An Archetype of Fish Alloherpesviruses.

    Science.gov (United States)

    Boutier, Maxime; Ronsmans, Maygane; Rakus, Krzysztof; Jazowiecka-Rakus, Joanna; Vancsok, Catherine; Morvan, Léa; Peñaranda, Ma Michelle D; Stone, David M; Way, Keith; van Beurden, Steven J; Davison, Andrew J; Vanderplasschen, Alain

    2015-01-01

    The order Herpesvirales encompasses viruses that share structural, genetic, and biological properties. However, members of this order infect hosts ranging from molluscs to humans. It is currently divided into three phylogenetically related families. The Alloherpesviridae family contains viruses infecting fish and amphibians. There are 12 alloherpesviruses described to date, 10 of which infect fish. Over the last decade, cyprinid herpesvirus 3 (CyHV-3) infecting common and koi carp has emerged as the archetype of fish alloherpesviruses. Since its first description in the late 1990s, this virus has induced important economic losses in common and koi carp worldwide. It has also had negative environmental implications by affecting wild carp populations. These negative impacts and the importance of the host species have stimulated studies aimed at developing diagnostic and prophylactic tools. Unexpectedly, the data generated by these applied studies have stimulated interest in CyHV-3 as a model for fundamental research. This review intends to provide a complete overview of the knowledge currently available on CyHV-3. © 2015 Elsevier Inc. All rights reserved.

  7. Novel heparan sulfate-binding peptides for blocking herpesvirus entry.

    Directory of Open Access Journals (Sweden)

    Pranay Dogra

    Full Text Available Human cytomegalovirus (HCMV infection can lead to congenital hearing loss and mental retardation. Upon immune suppression, reactivation of latent HCMV or primary infection increases morbidity in cancer, transplantation, and late stage AIDS patients. Current treatments include nucleoside analogues, which have significant toxicities limiting their usefulness. In this study we screened a panel of synthetic heparin-binding peptides for their ability to prevent CMV infection in vitro. A peptide designated, p5+14 exhibited ~ 90% reduction in murine CMV (MCMV infection. Because negatively charged, cell-surface heparan sulfate proteoglycans (HSPGs, serve as the attachment receptor during the adsorption phase of the CMV infection cycle, we hypothesized that p5+14 effectively competes for CMV adsorption to the cell surface resulting in the reduction in infection. Positively charged Lys residues were required for peptide binding to cell-surface HSPGs and reducing viral infection. We show that this inhibition was not due to a direct neutralizing effect on the virus itself and that the peptide blocked adsorption of the virus. The peptide also inhibited infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro, demonstrating it has broad-spectrum antiviral activity. Therefore, this peptide may offer an adjunct therapy for the treatment of herpes viral infections and other viruses that use HSPGs for entry.

  8. Membrane-Active Epithelial Keratin 6A Fragments (KAMPs) Are Unique Human Antimicrobial Peptides with a Non-αβ Structure

    Science.gov (United States)

    Lee, Judy T. Y.; Wang, Guangshun; Tam, Yu Tong; Tam, Connie

    2016-01-01

    Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs). Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS) micelles displayed amphipathic conformations with only local bends and turns, and a central 10-residue glycine-rich hydrophobic strip that is central to bactericidal activity. To our knowledge, this is the first report of non-αβ structure for human antimicrobial peptides. Direct observation of Staphylococcus aureus and Pseudomonas aeruginosa by scanning and transmission electron microscopy showed that KAMPs deformed bacterial cell envelopes and induced pore formation. Notably, in competitive binding experiments, KAMPs demonstrated binding affinities to LPS and LTA that did not correlate with their bactericidal activities, suggesting peptide-LPS and peptide-LTA interactions are less important in their mechanisms of action. Moreover, immunoprecipitation of KAMPs-bacterial factor complexes indicated that membrane surface lipoprotein SlyB and intracellular machineries NQR sodium pump and ribosomes are potential molecular targets for the peptides. Results of this study improve our understanding of the bactericidal function of epithelial cytokeratin fragments, and highlight an unexplored class of human antimicrobial peptides, which may serve as non-αβ peptide scaffolds for the design of novel peptide-based antibiotics. PMID:27891122

  9. Membrane-Active Epithelial Keratin 6A Fragments (KAMPs Are Unique Human Antimicrobial Peptides with a Non-αβ Structure

    Directory of Open Access Journals (Sweden)

    Judy Tsz Ying Lee

    2016-11-01

    Full Text Available Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs. Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS micelles displayed amphipathic conformations with only local bends and turns, and a central 10-residue glycine-rich hydrophobic strip that is central to bactericidal activity. To our knowledge, this is the first report of non-αβ structure for human antimicrobial peptides. Direct observation of Staphylococcus aureus and Pseudomonas aeruginosa by scanning and transmission electron microscopy showed that KAMPs deformed bacterial cell envelopes and induced pore formation. Notably, in competitive binding experiments, KAMPs demonstrated binding affinities to LPS and LTA that did not correlate with their bactericidal activities, suggesting peptide-LPS and peptide-LTA interactions are less important in their mechanisms of action. Moreover, immunoprecipitation of KAMPs-bacterial factor complexes indicated that membrane surface lipoprotein SlyB and intracellular machineries NQR sodium pump and ribosomes are potential molecular targets for the peptides. Results of this study improve our understanding of the bactericidal function of epithelial cytokeratin fragments, and highlight an unexplored class of human antimicrobial peptides, which may serve as non-αβ peptide scaffolds for the design of novel peptide-based antibiotics.

  10. The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

    DEFF Research Database (Denmark)

    Lüttichau, H R; Lewis, I C; Gerstoft, J

    2001-01-01

    The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both...

  11. Initial Detection and Molecular Characterization of Namaycush Herpesvirus (Salmonid Herpesvirus 5) in Lake Trout.

    Science.gov (United States)

    Glenney, Gavin W; Barbash, Patricia A; Coll, John A

    2016-03-01

    A novel herpesvirus was found by molecular methods in samples of Lake Trout Salvelinus namaycush from Lake Erie, Pennsylvania, and Lake Ontario, Keuka Lake, and Lake Otsego, New York. Based on PCR amplification and partial sequencing of polymerase, terminase, and glycoprotein genes, a number of isolates were identified as a novel virus, which we have named Namaycush herpesvirus (NamHV) salmonid herpesvirus 5 (SalHV5). Phylogenetic analyses of three NamHV genes indicated strong clustering with other members of the genus Salmonivirus, placing these isolates into family Alloherpesviridae. The NamHV isolates were identical in the three partially sequenced genes; however, they varied from other salmonid herpesviruses in nucleotide sequence identity. In all three of the genes sequenced, NamHV shared the highest sequence identity with Atlantic Salmon papillomatosis virus (ASPV; SalHV4) isolated from Atlantic Salmon Salmo salar in northern Europe, including northwestern Russia. These results lead one to believe that NamHV and ASPV have a common ancestor that may have made a relatively recent host jump from Atlantic Salmon to Lake Trout or vice versa. Partial nucleotide sequence comparisons between NamHV and ASPV for the polymerase and glycoprotein genes differ by >5% and >10%, respectively. Additional nucleotide sequence comparisons between NamHV and epizootic epitheliotropic disease virus (EEDV/SalHV3) in the terminase, glycoprotein, and polymerase genes differ by >5%, >20%, and >10%, respectively. Thus, NamHV and EEDV may be occupying discrete ecological niches in Lake Trout. Even though NamHV shared the highest genetic identity with ASPV, each of these viruses has a separate host species, which also implies speciation. Additionally, NamHV has been detected over the last 4 years in four separate water bodies across two states, which suggests that NamHV is a distinct, naturally replicating lineage. This, in combination with a divergence in nucleotide sequence from EEDV

  12. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    Science.gov (United States)

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

  13. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

    Science.gov (United States)

    Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

    2011-11-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

  14. Herpesvirus pan encodes a functional homologue of BHRF1, the Epstein-Barr virus v-Bcl-2

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    Williams Tracey

    2005-02-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV latently infects about 90% of the human population and is associated with benign and malignant diseases of lymphoid and epithelial origin. BHRF1, an early lytic cycle antigen, is an apoptosis suppressing member of the Bcl-2 family. In vitro studies imply that BHRF1 is dispensable for both virus replication and transformation. However, the fact that BHRF1 is highly conserved not only in all EBV isolates studied to date but also in the analogous viruses Herpesvirus papio and Herpesvirus pan that infect baboons and chimpanzees respectively, suggests BHRF1 may play an important role in vivo. Results Herpesvirus papio BHRF1 has been shown to function in an analogous manner to EBV BHRF1 in response to DNA damaging agents in human keratinocytes. In this study we show that the heterologous expression of the previously uncharacterised Herpesvirus pan BHRF1 in the human Burkitt's lymphoma cell line Ramos-BL provides similar anti-apoptotic functions to that of EBV BHRF1 in response to apoptosis triggered by serum withdrawal, etoposide treatment and ultraviolet (UV radiation. We also map the amino acid changes onto the recently solved structure of the EBV BHRF1 and reveal that these changes are unlikely to alter the 3D structure of the protein. Conclusions These findings show that the functional conservation of BHRF1 extends to a lymphoid background, suggesting that the primate virus proteins interact with cellular proteins that are themselves highly conserved across the higher primates. Further weight is added to this suggestion when we show that the difference in amino acid sequences map to regions on the 3D structure of EBV BHRF1 that are unlikely to change the conformation of the protein.

  15. Investigation of Koi Herpesvirus Latency in Koi▿

    Science.gov (United States)

    Eide, Kathleen E.; Miller-Morgan, Tim; Heidel, Jerry R.; Kent, Michael L.; Bildfell, Rob J.; LaPatra, Scott; Watson, Gregory; Jin, Ling

    2011-01-01

    Koi herpesvirus (KHV) has recently been classified as a member of the family of Alloherpesviridae within the order of Herpesvirales. One of the unique features of Herpesviridae is latent infection following a primary infection. However, KHV latency has not been recognized. To determine if latency occurs in clinically normal fish from facilities with a history of KHV infection or exposure, the presence of the KHV genome was investigated in healthy koi by PCR and Southern blotting. KHV DNA, but not infectious virus or mRNAs from lytic infection, was detected in white blood cells from investigated koi. Virus shedding was examined via tissue culture and reverse transcription-PCR (RT-PCR) testing of gill mucus and feces from six koi every other day for 1 month. No infectious virus or KHV DNA was detected in fecal secretion or gill swabs, suggesting that neither acute nor persistent infection was present. To determine if KHV latent infections can be reactivated, six koi were subjected to a temperature stress regime. KHV DNA and infectious virus were detected in both gill and fecal swabs by day 8 following temperature stress. KHV DNA was also detectable in brain, spleen, gills, heart, eye, intestine, kidney, liver, and pancreas in euthanized koi 1 month post-temperature stress. Our study suggests that KHV may become latent in leukocytes and other tissues, that it can be reactivated from latency by temperature stress, and that it may be more widespread in the koi population than previously suspected. PMID:21389134

  16. Identification of herpesvirus proteins that contribute to G1/S arrest.

    Science.gov (United States)

    Paladino, Patrick; Marcon, Edyta; Greenblatt, Jack; Frappier, Lori

    2014-04-01

    Lytic infection by herpesviruses induces cell cycle arrest at the G1/S transition. This appears to be a function of multiple herpesvirus proteins, but only a minority of herpesvirus proteins have been examined for cell cycle effects. To gain a more comprehensive understanding of the viral proteins that contribute to G1/S arrest, we screened a library of over 200 proteins from herpes simplex virus type 1, human cytomegalovirus, and Epstein-Barr virus (EBV) for effects on the G1/S interface, using HeLa fluorescent, ubiquitination-based cell cycle indicator (Fucci) cells in which G1/S can be detected colorimetrically. Proteins from each virus were identified that induce accumulation of G1/S cells, predominantly tegument, early, and capsid proteins. The identification of several capsid proteins in this screen suggests that incoming viral capsids may function to modulate cellular processes. The cell cycle effects of selected EBV proteins were further verified and examined for effects on p53 and p21 as regulators of the G1/S transition. Two EBV replication proteins (BORF2 and BMRF1) were found to induce p53 but not p21, while a previously uncharacterized tegument protein (BGLF2) was found to induce p21 protein levels in a p53-independent manner. Proteomic analyses of BGLF2-interacting proteins identified interactions with the NIMA-related protein kinase (NEK9) and GEM-interacting protein (GMIP). Silencing of either NEK9 or GMIP induced p21 without affecting p53 and abrogated the ability of BGLF2 to further induce p21. Collectively, these results suggest multiple viral proteins contribute to G1/S arrest, including BGLF2, which induces p21 levels likely by interfering with the functions of NEK9 and GMIP. Most people are infected with multiple herpesviruses, whose proteins alter the infected cells in several ways. During lytic infection, the viral proteins block cell proliferation just before the cellular DNA replicates. We used a novel screening method to identify proteins

  17. Herpesviruses in asymptomatic apical periodontitis lesions: an immunohistochemical approach.

    Science.gov (United States)

    Saboia-Dantas, C J; Coutrin de Toledo, L F; Sampaio-Filho, H R; Siqueira, J F

    2007-10-01

    Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been recently detected in samples from apical periodontitis lesions by means of molecular biology techniques and a role in the pathogenesis of this disease has been suggested. The present study was designed to survey asymptomatic primary apical periodontitis lesions for the presence of HCMV- and/or EBV-infected cells by means of immunohistochemistry. Apical periodontitis lesions were obtained from 35 patients [26 human immunodeficiency virus (HIV) -seronegative patients and nine HIV-seropositive patients] after tooth extraction and subjected to immunohistochemical analysis using monoclonal antibodies specific for HCMV and EBV. Fifteen of the 35 apical periodontitis lesions were positive for the target herpesviruses. Overall, EBV was found in 31% of the samples and HCMV in 23%, with 14% of the lesions showing EBV and HCMV dual infection. No association was found between HCMV or EBV with any particular histopathological type of apical periodontitis (P > 0.05). HCMV was significantly more frequent in apical periodontitis lesions from HIV-positive patients (67%) than in lesions from HIV-negative patients (8%) (P = 0.001). EBV was detected in 44% of lesions from HIV-positive patients and in 27% of lesions from HIV-negative patients, but this difference was not significant (P = 0.91). Our results showed that cells infected by HCMV and EBV can be found in apical periodontitis lesions, with a higher prevalence in HIV-positive patients. The specific role that these viruses play in the pathogenesis of apical periodontitis remains to be described.

  18. A Genomic Approach to Unravel Host-Pathogen Interaction in Chelonians: The Example of Testudinid Herpesvirus 3.

    Directory of Open Access Journals (Sweden)

    Francesco C Origgi

    Full Text Available We report the first de novo sequence assembly and analysis of the genome of Testudinid herpesvirus 3 (TeHV3, one of the most pathogenic chelonian herpesviruses. The genome of TeHV3 is at least 150,080 nucleotides long, is arranged in a type D configuration and comprises at least 102 open reading frames extensively co-linear with those of Human herpesvirus 1. Consistently, the phylogenetic analysis positions TeHV3 among the Alphaherpesvirinae, closely associated with Chelonid herpesvirus 5, a Scutavirus. To date, there has been limited genetic characterization of TeHVs and a resolution beyond the genotype was not feasible because of the lack of informative DNA sequences. To exemplify the potential benefits of the novel genomic information provided by this first whole genome analysis, we selected the glycoprotein B (gB gene, for detailed comparison among different TeHV3 isolates. The rationale for selecting gB is that it encodes for a well-conserved protein among herpesviruses but is coupled with a relevant antigenicity and is consequently prone to accumulate single nucleotide polymorphisms. These features were considered critical for an ideal phylogenetic marker to investigate the potential existence of distinct TeHV3 genogroups and their associated pathology. Fifteen captive tortoises presumptively diagnosed to be infected with TeHVs or carrying compatible lesions on the basis of either the presence of intranuclear inclusions (presumptively infected and/or diphtheronecrotic stomatitis-glossitis or pneumonia (compatible lesions were selected for the study. Viral isolation, TeHV identification, phylogenetic analysis and pathological characterization of the associated lesions, were performed. Our results revealed 1 the existence of at least two distinct TeHV3 genogroups apparently associated with different pathologies in tortoises and 2 the first evidence for a putative homologous recombination event having occurred in a chelonian herpesvirus. This

  19. A Genomic Approach to Unravel Host-Pathogen Interaction in Chelonians: The Example of Testudinid Herpesvirus 3

    Science.gov (United States)

    Origgi, Francesco C.; Tecilla, Marco; Pilo, Paola; Aloisio, Fabio; Otten, Patricia; Aguilar-Bultet, Lisandra; Sattler, Ursula; Roccabianca, Paola; Romero, Carlos H.; Bloom, David C.; Jacobson, Elliott R.

    2015-01-01

    We report the first de novo sequence assembly and analysis of the genome of Testudinid herpesvirus 3 (TeHV3), one of the most pathogenic chelonian herpesviruses. The genome of TeHV3 is at least 150,080 nucleotides long, is arranged in a type D configuration and comprises at least 102 open reading frames extensively co-linear with those of Human herpesvirus 1. Consistently, the phylogenetic analysis positions TeHV3 among the Alphaherpesvirinae, closely associated with Chelonid herpesvirus 5, a Scutavirus. To date, there has been limited genetic characterization of TeHVs and a resolution beyond the genotype was not feasible because of the lack of informative DNA sequences. To exemplify the potential benefits of the novel genomic information provided by this first whole genome analysis, we selected the glycoprotein B (gB) gene, for detailed comparison among different TeHV3 isolates. The rationale for selecting gB is that it encodes for a well-conserved protein among herpesviruses but is coupled with a relevant antigenicity and is consequently prone to accumulate single nucleotide polymorphisms. These features were considered critical for an ideal phylogenetic marker to investigate the potential existence of distinct TeHV3 genogroups and their associated pathology. Fifteen captive tortoises presumptively diagnosed to be infected with TeHVs or carrying compatible lesions on the basis of either the presence of intranuclear inclusions (presumptively infected) and/or diphtheronecrotic stomatitis-glossitis or pneumonia (compatible lesions) were selected for the study. Viral isolation, TeHV identification, phylogenetic analysis and pathological characterization of the associated lesions, were performed. Our results revealed 1) the existence of at least two distinct TeHV3 genogroups apparently associated with different pathologies in tortoises and 2) the first evidence for a putative homologous recombination event having occurred in a chelonian herpesvirus. This novel

  20. Prevalence of herpesviruses in gingivitis and chronic periodontitis: relationship to clinical parameters and effect of treatment

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    Rucha Shah

    2016-01-01

    Full Text Available Background: Assess the prevalence of herpesviruses in healthy subjects, gingivitis, and chronic periodontitis patients, to assess the relationship between the prevalence of herpesviruses and periodontal clinical parameters, and to evaluate the effect of phase-I therapy on the level of viral detection. Materials and Methods: Hundred patients consisting of 20 healthy subjects, 40 gingivitis, and 40 chronic periodontitis were included in the study. Clinical parameters recorded included plaque index, gingival index, sulcus bleeding index, probing depth, and clinical attachment level. The gingivitis and chronic periodontitis patients received phase-I periodontal therapy including oral hygiene instructions, full mouth scaling for gingivitis patients and scaling and root planing for chronic periodontitis patients. Gingival crevicular fluid (GCF was collected, and the presence of herpes simplex virus-1 (HSV-1, HSV-2, cytomegalovirus, and Epstein–Barr virus (EBV was analyzed using polymerase chain reaction (PCR. Recording of periodontal parameters as well as GCF collection was performed at baseline and 6 weeks postphase-I therapy. Results: At baseline, the levels of HSV-1 and EBV detection were lower in healthy controls as compared to gingivitis (P < 0.05 and chronic periodontitis cases (P < 0.001. Phase-I therapy led to reduction in the amount of HSV-1 and EBV in gingivitis patients (P < 0.05 and for HSV-1, human cytomegalovirus and EBV in chronic periodontitis patients (P < 0.05 in comparison to baseline. The prevalence of EBV in chronic periodontitis patients was positively associated with increased gingival index, probing depth and loss of clinical attachment (P < 0.05. Conclusions: Higher prevalence of HSV-1 and EBV viruses in GCF of gingivitis and chronic periodontitis suggests a strong association between these viruses and periodontal diseases and periodontal therapy can lead to a reduction in herpesviruses at infected sites.

  1. THE POSSIBILITIES OF MODERN DIAGNOSTICS OF HERPESVIRUS INFECTIONS IN CHILDREN

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    A. G. Bokovoy

    2013-01-01

    Full Text Available Medical history, clinical and laboratory data were studied in 828 children aged from 2 months to 14 years. All of them had different clinical forms of herpesvirus infections (HVI. The combination of the information allows to form the etiologic diagnosis timely and to evaluate the activity of the current infection. Given the polymorphism of clinical symptoms of HVI, it was very important to determine herpesvirus genomes in three media (blood, saliva, urine by PCR, and high titers of G-antibodies (439 u for CMV and 212.3 u for HHV-6. 

  2. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway

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    Gompels Ursula A

    2009-07-01

    Full Text Available Abstract Background Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked. Methods Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation. Results U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4

  3. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway.

    Science.gov (United States)

    Catusse, Julie; Clark, David J; Gompels, Ursula A

    2009-07-30

    Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A) infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked. Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation. U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4. U83A diverts human chemokines from signalling, but not

  4. THE IMPACT OF PERSISTENT HERPESVIRUS INFECTION ON IMMUNITY AND VACCINATION RESPONSE

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    Volyanskiy AYu

    2016-09-01

    Full Text Available In this review we summarize current knowledge on the ability of latent herpesviruses to modulate the immunity and response to vaccination. Nearly all humans are latently infected with multiple herpesviruses but little is known about virus-host interactions. Meanwhile, the study of the immune response to Epshtein-Barr virus (EBV and сytomegalovirus (CMV has revealed significant regulatory effects on the immune system. During the primary infection a human cytomegalovirus is predominately found in peripheral blood monocytes and polymorphonuclear leukocytes. However, the virus can not be replicated in these cells. CMV induces the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral replication and the release of virions, which infect CD34+ myeloid progenitor cells. CMV latently persists in myeloid progenitor cells and monocytes and reactivates during their differentiation into macrophages. CMV-infected monocytes exhibit a unique reprogramming of their differentiation and secret both pro-inflammatory M1- and anti-inflammatory M2-associated cytokines. But cytomegalovirus induced macrophage phenotype skewed towards pro-inflammatory M1 type. MV has profound effects on the composition and function of both T cells and NK cells. CMV constantly reactivates during differentiation of monocytes into macrophages. Consequently, persons with latent CMV infection have substantially increased numbers and proportions of CD8+ T cells that lead to exhaustion and an early onset of immunosenescence. Also, it has been shown that the latent CMV virus infection markedly increases the proportion of NK cells expressing the activating NKG2C receptor. So, it has been proposed that CMV alters the composition of T cell and NK cell subsets and accelerates immune aging. Given the capacity of CMV to alter a macrophage, as well as NK and T cell responses it is reasonable to hypothesize that latent infection would alter the

  5. The structures of bovine herpesvirus 1 virion and concatemeric DNA: implications for cleavage and packaging of herpesvirus genomes

    International Nuclear Information System (INIS)

    Schynts, Frederic; McVoy, Michael A.; Meurens, Francois; Detry, Bruno; Epstein, Alberto L.; Thiry, Etienne

    2003-01-01

    Herpesvirus genomes are often characterized by the presence of direct and inverted repeats that delineate their grouping into six structural classes. Class D genomes consist of a long (L) segment and a short (S) segment. The latter is flanked by large inverted repeats. DNA replication produces concatemers of head-to-tail linked genomes that are cleaved into unit genomes during the process of packaging DNA into capsids. Packaged class D genomes are an equimolar mixture of two isomers in which S is in either of two orientations, presumably a consequence of homologous recombination between the inverted repeats. The L segment remains predominantly fixed in a prototype (P) orientation; however, low levels of genomes having inverted L (I L ) segments have been reported for some class D herpesviruses. Inefficient formation of class D I L genomes has been attributed to infrequent L segment inversion, but recent detection of frequent inverted L segments in equine herpesvirus 1 concatemers [Virology 229 (1997) 415-420] suggests that the defect may be at the level of cleavage and packaging rather than inversion. In this study, the structures of virion and concatemeric DNA of another class D herpesvirus, bovine herpesvirus 1, were determined. Virion DNA contained low levels of I L genomes, whereas concatemeric DNA contained significant amounts of L segments in both P and I L orientations. However, concatemeric termini exhibited a preponderance of L termini derived from P isomers which was comparable to the preponderance of P genomes found in virion DNA. Thus, the defect in formation of I L genomes appears to lie at the level of concatemer cleavage. These results have important implications for the mechanisms by which herpesvirus DNA cleavage and packaging occur

  6. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

    International Nuclear Information System (INIS)

    Styles, Darrel K.; Tomaszewski, Elizabeth K.; Jaeger, Laurie A.; Phalen, David N.

    2004-01-01

    Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions

  7. Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.

    Science.gov (United States)

    Oskay, Tuğba; Karademir, Asli; Ertürk, Ozcan I

    2006-07-01

    Anticonvulsant hypersensitivity syndrome (AHS) is one of the most severe forms of drug eruption with potentially lethal, and multiorgan involvement. Recently, it has been suggested that Human Herpesvirus (HHV) infection has been involved in this syndrome, although the pathogenesis of this syndrome remains still unclear. The objective of this study was to determine the clinical characteristics of AHS and the possible role of viral infection as a co-factor. We prospectively analyzed clinical, laboratory and virological findings for 23 cases of AHS. A viral study including viral serology and a polymerase chain reaction (PCR) was performed. The most common anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS. Even though internal organ involvement such as liver (52%), kidney (34%), and lung (13%) has been observed, involvement of heart, lung, thyroid, muscle, pancreas, spleen, and brain was less frequent. We also noted two patients who died due to multiorgan failure. No association with viral infection including HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in 5 out of the 23 patients while HHV-7 was seen in two patients. We found an evidence to link reactivation of HHV-6 or HHV-7 in the development of only carbamazepine-induced AHS. We propose that some cases of AHS are accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may contribute to the severity, prolongation, or relapse of AHS and may possibly have fatal consequences in some susceptible individuals receiving the anticonvulsants.

  8. Dynamics of virus shedding and in situ confirmation of chelonid herpesvirus 5 in Hawaiian green turtles with Fibropapillomatosis

    Science.gov (United States)

    Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Schettle, Nelli; Ackermann, Mathias

    2015-01-01

    Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5.

  9. Dynamics of Virus Shedding and In Situ Confirmation of Chelonid Herpesvirus 5 in Hawaiian Green Turtles With Fibropapillomatosis.

    Science.gov (United States)

    Work, T M; Dagenais, J; Balazs, G H; Schettle, N; Ackermann, M

    2015-11-01

    Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5. © The Author(s) 2014.

  10. Seroprevalence and risk factors associated with bovine herpesvirus ...

    African Journals Online (AJOL)

    Bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus (BVDV) are well known etiological agents of cattle that produce important economic losses due to reproductive failures and calf mortality, as well as enteric and respiratory disease. Tamaulipas is located northeast of Mexico, an important cattle production and ...

  11. The impact of herpesviruses on reproductive performance in horses

    NARCIS (Netherlands)

    Schulman, Martin

    2016-01-01

    The thesis addresses the largely-undefined influence of the equine herpesviruses (EHVs) and in particular EHV-1 and -4 on reproductive performance in horse-breeding systems. These pathogens cause significant losses to the international equine breeding industry primarily through infectious abortion

  12. Structural and functional analysis of bovine herpesvirus 1 minor glycoproteins

    NARCIS (Netherlands)

    Baranowski, E.; Keil, G.; Lyaku, J.; Rijsewijk, F.A.M.; Oirschot, van J.T.; Pastoret, P.P.; Thiry, E.

    1996-01-01

    This paper focuses on the structure and functions of bovine herpesvirus 1 minor glycoproteins gH, gE, gG and gp42. It reviews the progress which has been made in their identification and characterization, in the study of their temporal expression and processing in infected cells, and finally in the

  13. The vaccines for Bovine Herpesvirus Type 1: A review | Zhao ...

    African Journals Online (AJOL)

    Bovine herpesvirus type 1 (BoHV-1) is the pathogen of Infectious Bovine Rhinothracheitis (IBR) disease, causing great economic losses in the livestock industry. Vaccine is a powerful means to control the virus. Here, the review described the currently available knowledge regarding to the advance in the field of BoHV-1 ...

  14. A simple method for purification of herpesvirus DNA

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Normann, Preben

    1992-01-01

    A rapid and reliable method for purification of herpesvirus DNA from cell cultures is described. The method is based on the isolation of virus particles and/or nucleocapsids by differential centrifugation and exploits the solubilizing and denaturing capabilities of cesium trifluoroacetate during...

  15. Advances in development and evaluation of bovine herpesvirus 1 vaccines

    NARCIS (Netherlands)

    Oirschot, van J.T.; Kaashoek, M.J.; Rijsewijk, F.A.M.

    1996-01-01

    This review deals with conventional and modern bovine herpesvirus 1 (BHV1) vaccines. Conventional vaccines are widely used to prevent clinical signs of infectious bovine rhinotracheitis. The use of conventional vaccines, however, does not appear to have resulted in reduction of the prevalence of

  16. CD1d expression and invariant NKT cell responses in herpesvirus infections

    Directory of Open Access Journals (Sweden)

    Rusung eTan

    2015-06-01

    Full Text Available Invariant natural killer T (iNKT cells are a highly conserved subset of unconventional T lymphocytes that express a canonical, semi-invariant T cell receptor (TCR and surface markers shared with the natural killer cell lineage. iNKT cells recognize exogenous and endogenous glycolipid antigens restricted by non-polymorphic CD1d molecules, and are highly responsive to the prototypical agonist, α-galactosylceramide. Upon activation, iNKT cells rapidly coordinate signaling between innate and adaptive immune cells through the secretion of proinflammatory cytokines, leading to the maturation of antigen-presenting cells and expansion of antigen-specific CD4+ and CD8+ T cells. Because of their potent immunoregulatory properties, iNKT cells have been extensively studied and are known to play a pivotal role in mediating immune responses against microbial pathogens including viruses. Here, we review evidence that herpesviruses manipulate CD1d expression to escape iNKT cell surveillance and establish lifelong latency in humans. Collectively, published findings suggest that iNKT cells play critical roles in anti-herpesvirus immune responses and could be harnessed therapeutically to limit viral infection and viral-associated disease.

  17. Naturally transmitted herpesvirus papio-2 infection in a black and white colobus monkey.

    Science.gov (United States)

    Troan, Brigid V; Perelygina, Ludmila; Patrusheva, Irina; Wettere, Arnaud J van; Hilliard, Julia K; Loomis, Michael R; Voe, Ryan S De

    2007-12-15

    A 6.5-year-old female eastern black and white colobus monkey (Colobus guereza) was evaluated after acute onset of ataxia and inappetence. The monkey was ataxic and lethargic, but no other abnormalities were detected via physical examination, radiography, or clinicopathologic analyses. During the next 2 days, the monkey's clinical condition deteriorated, and its WBC count decreased dramatically. Cytologic examination of a CSF sample revealed marked lymphohistiocytic inflammation. Despite supportive care, the monkey became apneic; after 20 hours of mechanical ventilation, fatal cardiac arrest occurred. At necropsy, numerous petechiae were detected within the white matter tracts of the brain; microscopic lesions of multifocal necrosis and hemorrhage with intranuclear inclusions identified in the brain and adrenal glands were consistent with an acute herpesvirus infection. A specific diagnosis of herpesvirus papio-2 (HVP-2) infection was made on the basis of results of serologic testing; PCR assay of tissue specimens; live virus isolation from the lungs; and immunohistochemical identification of the virus within brain, spinal cord, and adrenal gland lesions. Via phylogenetic tree analysis, the colobus HVP-2 isolate was grouped with neuroinvasive strains of the virus. The virus was most likely transmitted to the colobus monkey through toys shared with a nearby colony of baboons (the natural host of HVP-2). To the authors' knowledge, this is the first reported case of natural transmission of HVP-2 to a nonhost species. Infection with HVP-2 should be a differential diagnosis for acute encephalopathy in primate monkeys and humans, particularly following exposure to baboons.

  18. Biological and immunogenic properties of rabies virus glycoprotein expressed by canine herpesvirus vector.

    Science.gov (United States)

    Xuan, X; Tuchiya, K; Sato, I; Nishikawa, Y; Onoderaz, Y; Takashima, Y; Yamamoto, A; Katsumata, A; Iwata, A; Ueda, S; Mikami, T; Otsuka, H

    1998-01-01

    In order to evaluate whether canine herpesvirus (CHV) could be used as a live vector for the expression of heterologous immunogenes, we constructed a recombinant canine herpesvirus (CHV) expressing glycoprotein (G protein) of rabies virus (RV). The gene of G protein was inserted within the thymidine kinase gene of CHV YP11mu strain under the control of the human cytomegalovirus immediate early promoter. The G protein expressed by the recombinant CHV was processed and transported to the cell surface as in RV infected cells, and showed the same biological activities such as low pH dependent cell fusion and hemadsorption. The antigenic authenticity of the recombinant G protein was confirmed by a panel of monoclonal antibodies specific for G protein. Dogs inoculated intransally with the recombinant CHV produced higher titres of virus neutralizing antibodies against RV than those inoculated with a commercial, inactivated rabies vaccine. These results suggest that the CHV recombinant expressing G protein can be used as a vaccine to control canine rabies and that CHV may be useful as a vector to develop live recombinant against other infectious diseases in dogs.

  19. Multiplexed colorimetric detection of Kaposi's sarcoma associated herpesvirus and Bartonella DNA using gold and silver nanoparticles

    Science.gov (United States)

    Mancuso, Matthew; Jiang, Li; Cesarman, Ethel; Erickson, David

    2013-01-01

    Kaposi's sarcoma (KS) is an infectious cancer occurring most commonly in human immunodeficiency virus (HIV) positive patients and in endemic regions, such as Sub-Saharan Africa, where KS is among the top four most prevalent cancers. The cause of KS is the Kaposi's sarcoma-associated herpesvirus (KSHV, also called HHV-8), an oncogenic herpesvirus that while routinely diagnosed in developed nations, provides challenges to developing world medical providers and point-of-care detection. A major challenge in the diagnosis of KS is the existence of a number of other diseases with similar clinical presentation and histopathological features, requiring the detection of KSHV in a biopsy sample. In this work we develop an answer to this challenge by creating a multiplexed one-pot detection system for KSHV DNA and DNA from a frequently confounding disease, bacillary angiomatosis. Gold and silver nanoparticle aggregation reactions are tuned for each target and a multi-color change system is developed capable of detecting both targets down to levels between 1 nM and 2 nM. The system developed here could later be integrated with microfluidic sample processing to create a final device capable of solving the two major challenges in point-of-care KS detection.

  20. Functional homology of gHs and gLs from EBV-related γ-herpesviruses for EBV-induced membrane fusion

    International Nuclear Information System (INIS)

    Omerovic, Jasmina; Longnecker, Richard

    2007-01-01

    Epstein-Barr virus (EBV) is a human γ-herpesvirus that primarily infects B lymphocytes and epithelial cells. Entry of EBV into B cells requires the viral glycoproteins gp42, gH/gL and gB, while gp42 is not necessary for infection of epithelial cells. In EBV, gH and gL form two distinct complexes, a bipartite complex that contains only gH and gL, used for infection of epithelial cells, and a tripartite complex that additionally includes gp42, used for infection of B cells. The gH/gL complex is conserved within the herpesvirus family, but its exact role in entry and mechanism of fusion is not yet known. To understand more about the functionality of EBVgH/gL, we investigated the functional homology of gHs and gLs from human herpesvirus 8 (HHV8) and two primate (rhesus and marmoset) γ-herpesviruses in EBV-mediated virus-free cell fusion assay. Overall, gHs and gLs from the more homologous primate herpesviruses were better at complementing EBV gH and gL in fusion than HHV8 gH and gL. Interestingly, marmoset gH was able to complement fusion with epithelial cells, but not B cells. Further investigation of this led to the discovery that EBVgH is the binding partner of gp42 in the tripartite complex and the absence of fusion with B cells in the presence of marmoset gH/gL is due to its inability to bind gp42

  1. Detection of testudinid herpesvirus type 4 in a leopard tortoise (Stigmochelys pardalis).

    Science.gov (United States)

    Kolesnik, Ekaterina; Mittenzwei, Frank; Marschang, Rachel E

    2016-08-17

    Several animals from a mixed species collection of tortoises in Germany died unexpectedly. Some of the affected leopard tortoises (Stigmochelys pardalis) from this group showed respiratory signs. Samples were collected from one of the ill tortoises, and a Mycoplasma spp. and a herpesvirus were detected by PCR. Sequencing of a portion of the DNA polymerase gene of the herpesvirus showed 99% identity with testudinid herpesvirus 4, previously described only once in a bowsprit tortoise (Chersina angulata) in the United States.

  2. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Chiara Pratesi

    Full Text Available Autologous stem cell transplantation (ASCT is a feasible procedure for human immunodeficiency virus-1 (HIV-1 lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV- and Kaposi sarcoma-associated herpesvirus (KSHV-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs of 12 (median 12,135 copies/mL and 18 patients (median 417 copies/10(6 PBMCs, respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001. Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03 and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04. After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.

  3. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G

    2005-01-01

    Kaposi's sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively...

  4. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    OpenAIRE

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2...

  5. The Role of microRNAs in the Pathogenesis of Herpesvirus Infection.

    Science.gov (United States)

    Piedade, Diogo; Azevedo-Pereira, José Miguel

    2016-06-02

    MicroRNAs (miRNAs) are small non-coding RNAs important in gene regulation. They are able to regulate mRNA translation through base-pair complementarity. Cellular miRNAs have been involved in the regulation of nearly all cellular pathways, and their deregulation has been associated with several diseases such as cancer. Given the importance of microRNAs to cell homeostasis, it is no surprise that viruses have evolved to take advantage of this cellular pathway. Viruses have been reported to be able to encode and express functional viral microRNAs that target both viral and cellular transcripts. Moreover, viral inhibition of key proteins from the microRNA pathway and important changes in cellular microRNA pool have been reported upon viral infection. In addition, viruses have developed multiple mechanisms to avoid being targeted by cellular microRNAs. This complex interaction between host and viruses to control the microRNA pathway usually favors viral infection and persistence by either reducing immune detection, avoiding apoptosis, promoting cell growth, or promoting lytic or latent infection. One of the best examples of this virus-host-microRNA interplay emanates from members of the Herperviridae family, namely the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), human cytomegalovirus (HCMV), human herpesvirus 8 (HHV-8), and the Epstein-Barr virus (EBV). In this review, we will focus on the general functions of microRNAs and the interactions between herpesviruses, human hosts, and microRNAs and will delve into the related mechanisms that contribute to infection and pathogenesis.

  6. Central nervous system disease and genital disease in harbor porpoises (Phocoena phocoena) are associated with different herpesviruses

    NARCIS (Netherlands)

    C.E. van Elk; M.W.G. van de Bildt (Marco); P.R.W.A. van Run (Peter); De Jong, A. (Anton); S. Getu (Sarah); G.M.G.M. Verjans (George); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2016-01-01

    textabstractHerpesvirus infection causes disease of variable severity in many species, including cetaceans. However, little is known about herpesvirus infection in harbor porpoises (Phocoena phocoena), despite being widespread in temperate coastal waters of the Northern Hemisphere. Therefore, we

  7. Dyscoria associated with herpesvirus infection in owl monkeys (Aotus nancymae)

    Energy Technology Data Exchange (ETDEWEB)

    Gozalo, Alfonso S.; Montoya, Enrique J.; Weller, Richard E.

    2008-08-16

    Abstract Dyscoria was observed in a female owl monkey and her two offspring. A third offspring was found dead with necrohemorrhagic encephalitis. Two males paired with the female died, one of which showed oral ulcers at necropsy. Histologic examination of the oral ulcers revealed syncytia and eosinophilic intranuclear inclusion bodies in epithelial cells. Ocular examination revealed posterior synechia associated with the dyscoria in all three animals. Serum samples from the female and her offspring were positive for Herpesvirus simplex antibodies by enzyme-linked immunosorbent assay. The clinical history, gross and microscopic lesions, and serology results suggests a herpesviral etiology, possibly, H. simplex or H. saimiri-1. This report underscores the risks associated with introducing animals into breeding or research colonies that were previously kept as pets or those from unknown origin that could carry asymptomatic pathogenic Herpesvirus infections. In addition, herpesviral infection should be considered among the differential diagnoses if dyscoria is observed in nonhuman primates.

  8. Murid herpesvirus-4 exploits dendritic cells to infect B cells.

    Directory of Open Access Journals (Sweden)

    Miguel Gaspar

    2011-11-01

    Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

  9. Herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion.

    Directory of Open Access Journals (Sweden)

    Daniel L Glauser

    Full Text Available Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4 entry machinery--gB, gH/gL and gp150--changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion.

  10. Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain

    Directory of Open Access Journals (Sweden)

    Jason R. Andrews

    2011-01-01

    Full Text Available Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV. The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD, primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

  11. Antiviral activity of exopolysaccharides from Arthrospira platensis against koi herpesvirus.

    Science.gov (United States)

    Reichert, M; Bergmann, S M; Hwang, J; Buchholz, R; Lindenberger, C

    2017-10-01

    Although koi herpesvirus (KHV) has a history of causing severe economic losses in common carp and koi farms, there are still no treatments available on the market. Thus, the aim of this study was to test exopolysaccharides (EPS) for its antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in common carp brain cells. These substances can be easily extracted from extracellular algae supernatant and were identified as groups of sulphated polysaccharides. In order to reach this aim, Arthrospira platensis, which is well known for its antiviral activity of intra- and extracellular compounds towards mammalian herpesviruses, was investigated as standard organism and compared to commercial antiviral drug, ganciclovir, which inhibits the viral DNA polymerization. The antiviral activity of polysaccharides of A. platensis against KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes, and it was found by RT-PCR that EPS, applied at a concentration of >18 μg mL -1 and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral replication in common carp brain (CCB) cells even after 22 days post-infection, entirely. Further, this study presents first data indicating an enormous potential using polysaccharides as an additive for aquacultures to lower or hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future. © 2017 John Wiley & Sons Ltd.

  12. Prevalence and Clinical Significance of Herpesvirus Infection in Populations of Australian Marsupials.

    Directory of Open Access Journals (Sweden)

    Kathryn Stalder

    Full Text Available Herpesviruses have been reported in several marsupial species, but molecular classification has been limited to four herpesviruses in macropodids, a gammaherpesvirus in two antechinus species (Antechinus flavipes and Antechinus agilis, a gammaherpesvirus in a potoroid, the eastern bettong (Bettongia gaimardi and two gammaherpesviruses in koalas (Phascolarctos cinereus. In this study we examined a range of Australian marsupials for the presence of herpesviruses using molecular and serological techniques, and also assessed risk factors associated with herpesvirus infection. Our study population included 99 koalas (Phascolarctos cinereus, 96 eastern grey kangaroos (Macropus giganteus, 50 Tasmanian devils (Sarcophilus harrisii and 33 common wombats (Vombatus ursinius. In total, six novel herpesviruses (one alphaherpesvirus and five gammaherpesviruses were identified in various host species. The overall prevalence of detection of herpesvirus DNA in our study population was 27.2% (95% confidence interval (CI of 22.6-32.2%, but this varied between species and reached as high as 45.4% (95% CI 28.1-63.7% in common wombats. Serum antibodies to two closely related macropodid herpesviruses (macropodid herpesvirus 1 and 2 were detected in 44.3% (95% CI 33.1-55.9% of animals tested. This also varied between species and was as high as 92% (95% CI 74.0-99.0% in eastern grey kangaroos. A number of epidemiological variables were identified as positive predictors for the presence of herpesvirus DNA in the marsupial samples evaluated. The most striking association was observed in koalas, where the presence of Chlamydia pecorum DNA was strongly associated with the presence of herpesvirus DNA (Odds Ratio = 60, 95% CI 12.1-297.8. Our results demonstrate the common presence of herpesviruses in Australian marsupials and provide directions for future research.

  13. Prevalence and Clinical Significance of Herpesvirus Infection in Populations of Australian Marsupials.

    Science.gov (United States)

    Stalder, Kathryn; Vaz, Paola K; Gilkerson, James R; Baker, Rupert; Whiteley, Pam; Ficorilli, Nino; Tatarczuch, Liliana; Portas, Timothy; Skogvold, Kim; Anderson, Garry A; Devlin, Joanne M

    2015-01-01

    Herpesviruses have been reported in several marsupial species, but molecular classification has been limited to four herpesviruses in macropodids, a gammaherpesvirus in two antechinus species (Antechinus flavipes and Antechinus agilis), a gammaherpesvirus in a potoroid, the eastern bettong (Bettongia gaimardi) and two gammaherpesviruses in koalas (Phascolarctos cinereus). In this study we examined a range of Australian marsupials for the presence of herpesviruses using molecular and serological techniques, and also assessed risk factors associated with herpesvirus infection. Our study population included 99 koalas (Phascolarctos cinereus), 96 eastern grey kangaroos (Macropus giganteus), 50 Tasmanian devils (Sarcophilus harrisii) and 33 common wombats (Vombatus ursinius). In total, six novel herpesviruses (one alphaherpesvirus and five gammaherpesviruses) were identified in various host species. The overall prevalence of detection of herpesvirus DNA in our study population was 27.2% (95% confidence interval (CI) of 22.6-32.2%), but this varied between species and reached as high as 45.4% (95% CI 28.1-63.7%) in common wombats. Serum antibodies to two closely related macropodid herpesviruses (macropodid herpesvirus 1 and 2) were detected in 44.3% (95% CI 33.1-55.9%) of animals tested. This also varied between species and was as high as 92% (95% CI 74.0-99.0%) in eastern grey kangaroos. A number of epidemiological variables were identified as positive predictors for the presence of herpesvirus DNA in the marsupial samples evaluated. The most striking association was observed in koalas, where the presence of Chlamydia pecorum DNA was strongly associated with the presence of herpesvirus DNA (Odds Ratio = 60, 95% CI 12.1-297.8). Our results demonstrate the common presence of herpesviruses in Australian marsupials and provide directions for future research.

  14. Prevalence and Clinical Significance of Herpesvirus Infection in Populations of Australian Marsupials

    Science.gov (United States)

    Stalder, Kathryn; Vaz, Paola K.; Gilkerson, James R.; Baker, Rupert; Whiteley, Pam; Ficorilli, Nino; Tatarczuch, Liliana; Portas, Timothy; Skogvold, Kim; Anderson, Garry A.; Devlin, Joanne M.

    2015-01-01

    Herpesviruses have been reported in several marsupial species, but molecular classification has been limited to four herpesviruses in macropodids, a gammaherpesvirus in two antechinus species (Antechinus flavipes and Antechinus agilis), a gammaherpesvirus in a potoroid, the eastern bettong (Bettongia gaimardi) and two gammaherpesviruses in koalas (Phascolarctos cinereus). In this study we examined a range of Australian marsupials for the presence of herpesviruses using molecular and serological techniques, and also assessed risk factors associated with herpesvirus infection. Our study population included 99 koalas (Phascolarctos cinereus), 96 eastern grey kangaroos (Macropus giganteus), 50 Tasmanian devils (Sarcophilus harrisii) and 33 common wombats (Vombatus ursinius). In total, six novel herpesviruses (one alphaherpesvirus and five gammaherpesviruses) were identified in various host species. The overall prevalence of detection of herpesvirus DNA in our study population was 27.2% (95% confidence interval (CI) of 22.6–32.2%), but this varied between species and reached as high as 45.4% (95% CI 28.1–63.7%) in common wombats. Serum antibodies to two closely related macropodid herpesviruses (macropodid herpesvirus 1 and 2) were detected in 44.3% (95% CI 33.1–55.9%) of animals tested. This also varied between species and was as high as 92% (95% CI 74.0–99.0%) in eastern grey kangaroos. A number of epidemiological variables were identified as positive predictors for the presence of herpesvirus DNA in the marsupial samples evaluated. The most striking association was observed in koalas, where the presence of Chlamydia pecorum DNA was strongly associated with the presence of herpesvirus DNA (Odds Ratio = 60, 95% CI 12.1–297.8). Our results demonstrate the common presence of herpesviruses in Australian marsupials and provide directions for future research. PMID:26222660

  15. Homologous and heterologous antibody responses of mice immunized with purified feline herpesvirus type 1 and canine herpesvirus glycoproteins.

    Science.gov (United States)

    Limcumpao, J A; Horimoto, T; Xuan, X N; Tohya, Y; Azetaka, M; Takahashi, E; Mikami, T

    1991-06-01

    The three glycoproteins each of feline herpesvirus type 1 (FHV-1) and canine herpesvirus (CHV) were purified by affinity chromatography using glycoprotein-specific monoclonal antibodies and used individually or in combination in immunizing mice to determine their relative immunogenicity. All the glycoproteins induced detectable virus neutralizing antibodies to the homologous virus but FHV-1 gp143/108 and its cross-reacting counterpart, CHV gp145/112, elicited the highest titers not only to the homologous virus but to the heterologous virus as well. The production of ELISA antibodies after glycoprotein immunization was variable, while hemagglutination-inhibiting antibodies were produced by only 1 out of 10 FHV-1 gp60-inoculated mice. In general, the antibody titers induced by CHV glycoproteins were lower than those by FHV-1 glycoproteins. These results indicate that these glycoproteins may be useful as subunit vaccines against FHV-1 and CHV infections.

  16. Genetic variation and dynamics of infections of equid herpesvirus 5 in individual horses.

    Science.gov (United States)

    Back, Helena; Ullman, Karin; Leijon, Mikael; Söderlund, Robert; Penell, Johanna; Ståhl, Karl; Pringle, John; Valarcher, Jean-François

    2016-01-01

    Equid herpesvirus 5 (EHV-5) is related to the human Epstein-Barr virus (human herpesvirus 4) and has frequently been observed in equine populations worldwide. EHV-5 was previously assumed to be low to non-pathogenic; however, studies have also related the virus to the severe lung disease equine multinodular pulmonary fibrosis (EMPF). Genetic information of EHV-5 is scanty: the whole genome was recently described and only limited nucleotide sequences are available. In this study, samples were taken twice 1 year apart from eight healthy horses at the same professional training yard and samples from a ninth horse that was diagnosed with EMPF with samples taken pre- and post-mortem to analyse partial glycoprotein B (gB) gene of EHV-5 by using next-generation sequencing. The analysis resulted in 27 partial gB gene sequences, 11 unique sequence types and five amino acid sequences. These sequences could be classified within four genotypes (I-IV) of the EHV-5 gB gene based on the degree of similarity of the nucleotide and amino acid sequences, and in this work horses were shown to be identified with up to three different genotypes simultaneously. The observations showed a range of interactions between EHV-5 and the host over time, where the same virus persists in some horses, whereas others have a more dynamic infection pattern including strains from different genotypes. This study provides insight into the genetic variation and dynamics of EHV-5, and highlights that further work is needed to understand the EHV-5 interaction with its host.

  17. The Complete Genome Sequence of Herpesvirus Papio 2 (Cercopithecine Herpesvirus 16) Shows Evidence of Recombination Events among Various Progenitor Herpesviruses†

    Science.gov (United States)

    Tyler, Shaun D.; Severini, Alberto

    2006-01-01

    We have sequenced the entire genome of herpesvirus papio 2 (HVP-2; Cercopithecine herpesvirus 16) strain X313, a baboon herpesvirus with close homology to other primate alphaherpesviruses, such as SA8, monkey B virus, and herpes simplex virus (HSV) type 1 and type 2. The genome of HVP-2 is 156,487 bp in length, with an overall GC content of 76.5%. The genome organization is identical to that of the other members of the genus Simplexvirus, with a long and a short unique region, each bordered by inverted repeats which end with an “a” sequence. All of the open reading frames detected in this genome were homologous and colinear with those of SA8 and B virus. The HSV gene RL1 (γ134.5; neurovirulence factor) is not present in HVP-2, as is the case for SA8 and B virus. The HVP-2 genome is 85% homologous to its closest relative, SA8. However, segment-by-segment bootstrap analysis of the genome revealed at least two regions that display closer homology to the corresponding sequences of B virus. The first region comprises the UL41 to UL44 genes, and the second region is located within the UL36 gene. We hypothesize that this localized and defined shift in homology is due to recombination events between an SA8-like progenitor of HVP-2 and a herpesvirus species more closely related to the B virus. Since some of the genes involved in these putative recombination events are determinants of virulence, a comparative analysis of their function may provide insight into the pathogenic mechanism of simplexviruses. PMID:16414998

  18. Evaluation of metaphylactic RNA interference to prevent equine herpesvirus type 1 infection in experimental herpesvirus myeloencephalopathy in horses.

    Science.gov (United States)

    Perkins, Gillian A; Van de Walle, Gerlinde R; Pusterla, Nicola; Erb, Hollis N; Osterrieder, Nikolaus

    2013-02-01

    To evaluate metaphylactic RNA interference to prevent equine herpesvirus type 1 (EHV-1) infection in experimental herpesvirus myeloencephalopathy in horses and to determine whether horses infected with a neuropathogenic strain of the virus that develop equine herpesvirus myeloencephalopathy (EHM) have differences in viremia. 13 seronegative horses. EHV-1 strain Ab4 was administered intranasally on day 0, and small interfering RNAs (siRNAs [EHV-1 specific siRNAs {n = 7} or an irrelevant siRNA {6}]) were administered intranasally 24 hours before and 12, 24, 36, and 48 hours after infection. Physical and neurologic examinations, nasal swab specimens, and blood samples were collected for virus isolation and quantitative PCR assay. Data from the study were combined with data from a previous study of 14 horses. No significant difference was detected in clinical variables, viremia, or detection of EHV-1 in nasal swab specimens of horses treated with the EHV-1 targeted siRNAs (sigB3-siOri2) versus controls. No significant differences in viremia were detected between horses that developed EHM and those that did not. Administration of siRNAs targeted against EHV-1 around the time of EHV-1 infection was not protective with this experimental design. Horses infected with the neuropathogenic EHV-1 strain Ab4 that developed EHM did not have a more pronounced viremia.

  19. Prolonged persistence of bovine herpesvirus in small cattle herds: a model-based analysis

    NARCIS (Netherlands)

    Mollema, E.; Jong, de M.C.M.; Boven, van R.M.

    2005-01-01

    Herpesviruses can remain dormant in once-infected hosts and, upon reactivation, cause such hosts to become infectious. This phenomenon of latency and reactivation may enable herpesviruses to persist for a long time in small host populations. To quantify the effect of reactivation on persistence, the

  20. Identification and localization of the structural proteins of anguillid herpesvirus 1

    NARCIS (Netherlands)

    Beurden, van S.J.; Leroy, B.; Wattiez, R.; Haenen, O.L.M.; Boeren, S.; Vervoort, J.J.M.; Peeters, B.P.H.; Rottier, P.J.M.; Engelsma, M.Y.; Vanderplasschen, A.F.

    2011-01-01

    Many of the known fish herpesviruses have important aquaculture species as their natural host, and may cause serious disease and mortality. Anguillid herpesvirus 1 (AngHV-1) causes a hemorrhagic disease in European eel, Anguilla anguilla. Despite their importance, fundamental molecular knowledge on

  1. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    NARCIS (Netherlands)

    Zeev-Ben-Mordehai, Tzviya; Weberruss, Marion; Lorenz, Michael; Cheleski, Juliana; Hellberg, Teresa; Whittle, Cathy; El Omari, Kamel; Vasishtan, Daven; Dent, Kyle C.; Harlos, Karl; Franzke, Kati; Hagen, Christoph; Klupp, Barbara G.; Antonin, Wolfram; Mettenleiter, Thomas C.; Gruenewald, Kay

    2015-01-01

    Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC), which, in turn, mediates

  2. Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents.

    Science.gov (United States)

    Perelló M, Christie; Fernández-Carrillo, Carlos; Londoño, María-Carlota; Arias-Loste, Teresa; Hernández-Conde, Marta; Llerena, Susana; Crespo, Javier; Forns, Xavier; Calleja, José Luis

    2016-11-01

    We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Putative periodontopathic bacteria and herpesviruses in pregnant women: a case-control study

    OpenAIRE

    Lu, Haixia; Zhu, Ce; Li, Fei; Xu, Wei; Tao, Danying; Feng, Xiping

    2016-01-01

    Little is known about herpesvirus and putative periodontopathic bacteria in maternal chronic periodontitis. The present case-control study aimed to explore the potential relationship between putative periodontopathic bacteria and herpesviruses in maternal chronic periodontitis.Saliva samples were collected from 36 pregnant women with chronic periodontitis (cases) and 36 pregnant women with healthy periodontal status (controls). Six putative periodontopathic bacteria (Porphyromonas gingivalis ...

  4. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  5. Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

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    S. Ramos-da-Silva

    2006-05-01

    Full Text Available Kaposi's sarcoma (KS became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2% cases of classical KS, 29 (56.9% of AIDS-associated KS and 2 (3.9% of iatrogenic KS. Most patients were males (7.5:1, M/F, and mean age was 47.9 years (SD = ± 18.7 years. As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque compared to classical KS patients (predominantly nodular lesions. This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%, irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

  6. Asociación del virus herpes humano 8 y la hiperplasia linfoide nodular difusa del intestino delgado en la inmunodeficiencia variable común Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Elena Kokuina

    2009-12-01

    hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20+ and T cells (CD3+, similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR method detected many copies from the genome of type 8 human herpesvirus (VHH-8 (133 copies/µL of DNA in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID.

  7. Prevalence of Porphyromonas gingivalis and its relationship with herpesvirus in Indian subjects with chronic periodontitis: A cross-sectional study

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    Vinayak M Joshi

    2016-01-01

    Full Text Available Background: Porphyromonas gingivalis (P. gingivalis is a periodontal pathogen that is commonly harbored in the dental plaque of humans. The aim of this study was to look into the prevalence of P. gingivalis and its association with herpesvirus in Indian subjects. This is probably the first study on the association of this bacterium with herpesvirus in Indians. Materials and Methods: This cross-sectional study consists of 200 subjects, with 100 subjects each in the healthy group and the chronic periodontitis (CP group. Upon plaque collection, one portion of the samples was immediately plated, on culture media that is selective for P. gingivalis. Total colony-forming units (CFU/mL from each plate was recorded. The remaining plaque sample was subjected to DNA extraction and polymerase chain reaction (PCR was performed using specific primers for Cytomegalovirus (CMV and Epstein–Barr virus (EBV. The data are analyzed using the chi-square test, Spearman's rho correlation coefficient, and Mann–Whitney U test. Results: P. gingivalis was detected in 66% of the subjects with CP and in 40% in the healthy group, and this difference was statistically significant (P = 0.00023. The correlation of clinical parameters with P. gingivalis showed a significant positive correlation, indicating that higher levels of clinical parameters were associated with higher CFUs of P. gingivalis in culture. The comparison of the presence of P. gingivalis between herpesvirus-negative and -positive cases showed that CMV-positive cases had significantly higher levels of this bacterium. Conclusions: The results of this study confirmed the earlier finding of P. gingivalis presence in significantly higher levels in CP subjects and in CMV-positive sites. In addition, there was a positive association of the bacterium with clinical parameters.

  8. Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and Lck-dependent apoptosis of T lymphocytes

    International Nuclear Information System (INIS)

    Hasham, Muneer G.; Tsygankov, Alexander Y.

    2004-01-01

    Saimiriine herpesvirus-2 (Herpesvirus saimiri) transforms T lymphocytes, including human, to continuous growth in vitro. H. saimiri-induced transformation is becoming an important tool of T-cell biology, including studies of HIV replication. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T-cell transformation. In spite of the important role of these proteins, their biological functions and the molecular mechanisms of their action remain insufficiently understood. To further elucidate the effects of Tip on T cells, we transduced T lymphocytes, using an efficient lentiviral gene transfer system, to express Tip in the absence of other H. saimiri proteins. Our results indicate that Tip specifically inhibits IL-2 production by human T lymphocytes. Furthermore, Tip promotes T-cell apoptosis, which appears to be the reason for the observed decrease in IL-2 production. Finally, the apoptotic effect of Tip in T cells is mediated by Fas and requires the presence of active Lck in the cell

  9. CyHV-3: the third cyprinid herpesvirus.

    Science.gov (United States)

    Gotesman, Michael; Kattlun, Julia; Bergmann, Sven M; El-Matbouli, Mansour

    2013-07-22

    Common carp (including ornamental koi carp) Cyprinus carpio L. are ecologically and economically important freshwater fish in Europe and Asia. C. carpio have recently been endangered by a third cyprinid herpesvirus, known as cyprinid herpesvirus-3 (CyHV-3), the etiological agent of koi herpesvirus disease (KHVD), which causes significant morbidity and mortality in koi and common carp. Clinical and pathological signs include epidermal abrasions, excess mucus production, necrosis of gill and internal organs, and lethargy. KHVD has decimated major carp populations in Israel, Indonesia, Taiwan, Japan, Germany, Canada, and the USA, and has been listed as a notifiable disease in Germany since 2005, and by the World Organisation for Animal Health since 2007. KHVD is exacerbated in aquaculture because of the relatively high host stocking density, and CyHV-3 may be concentrated by filter-feeding aquatic organisms. CyHV-3 is taxonomically grouped within the family Alloherpesviridae, can be propagated in a number of cell lines, and is active at a temperature range of 15 to 28°C. Three isolates originating from Japan (KHV-J), USA (KHV-U), and Israel (KHV-I) have been sequenced. CyHV-3 has a 295 kb genome with 156 unique open reading frames and replicates in the cell nucleus, and mature viral particles are 170 to 200 nm in diameter. CyHV-3 can be detected by multiple PCR-based methods and by enzyme-linked immunosorbent assay. Several modes of immunization have been developed for KHVD; however, fish immunized with either vaccine or wild-type virus may become carriers for CyHV-3. There is no current treatment for KHVD.

  10. Cryo-gamma radiation inactivation of bovine herpesvirus type-1

    Science.gov (United States)

    Degiorgi, C. Fernández; Smolko, E. E.; Lombardo, J. H.

    1999-07-01

    The radioresistance of bovine herpesvirus-1 (BHV-1), commonly known as infectious bovine rhinotracheitis virus (IBRV), suspended in free serum Glasgow-MEM medium and frozen at -78°C was studied. The number of surviving virus at a given dose of gamma-radiation was determined by a plaque assay system. D 10 values were calculated before and after removal of cell debris. The D 10 values obtained were 4.72 kGy and 7.31 kGy before and after removal of cell debris, respectively. Our results indicate that the inactivated viral particles could be used for vaccine preparation or diagnostic reagents.

  11. Incidence of elephant endotheliotropic herpesvirus in Asian elephants in India.

    Science.gov (United States)

    Barman, Nagendra N; Choudhury, Bhaskar; Kumar, Vishnu; Koul, Monika; Gogoi, Sophia M; Khatoon, Elina; Chakroborty, A; Basumatary, P; Barua, B; Rahman, T; Das, S K; Kumar, Sachin

    2017-09-01

    Elephant endotheliotropic herpesviruses (EEHVs) are the cause of acute hemorrhagic disease in endangered Asian and African elephants. In the present study, we report the incidence of EEHV infection and associated mortality in the captive elephant of Assam, India. Our result showed the gross morphology and histopathological changes of EEHV infection in the elephant. Moreover, the phylogenetic analysis of the polymerase, helicase, and GPCR genes from the infected tissue samples suggested the presence of EEHV1A virus. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Herpesvirus canino 1: agente etiológico y enfermedad

    OpenAIRE

    Galosi, Cecilia Mónica

    2007-01-01

    El herpesvirus canino 1 es un alphaherpesvirus del cual se describe un solo serotipo. Este virus fue aislado en varios paises y en Europa es enzoótico en la población canina. Es uno de los principales agentes infecciosos relacionados a lesiones vesiculares en mucosas genitales y es causante de desórdenes reproductivos en caninos tales como reabsorciones fetales, abortos y muertes perinatales. Participa ocasionalmente como causante de la denominada Tos de las Perreras. Epidemiológicamente revi...

  13. The expression and serological reactivity of recombinant canine herpesvirus 1 glycoprotein D

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    MarkéŽta Vaňkov‡á

    2016-01-01

    Full Text Available The aim of this work was to express recombinant glycoprotein D of canine herpesvirus 1 in bacterial cells and to evaluate its diagnostic sensitivity and specificity when compared to traditional serological methods. The gene fragment coding glycoprotein D of canine herpesvirus 1 was amplified by polymerase chain reaction, cloned into plasmid vector and expressed in Escherichia coli cells. Recombinant protein was then purified and used as an antigen in immunoblot for a detection of canine herpesvirus 1 specific antibodies. Antibody testing was performed on the panel of 100 canine sera by immunoblot with recombinant glycoprotein D as antigen and compared with indirect immunofluorescence assay. Serum samples were collected from 83 dogs with no history of canine herpesvirus 1 or reproductive disorders, and from 17 dogs from breeding kennels with a history of canine herpesvirus 1 related reproductive disorders. Sensitivity of glycoprotein D based immunoblot was 89.2% and specificity was 93%. Kappa value was calculated to be 0.8 between immunoblot and indirect immunofluorescence assay. Antibodies against canine herpesvirus 1 infection were detected in 33% of samples by immunoblot assay. Our study confirms that recombinant glycoprotein D expressed in bacterial cells could be used as a suitable and sensitive antigen for immunological tests and that herpesvirus infection seems to be common among the canine population in the Czech Republic.

  14. Coordinated and sequential transcription of the cyprinid herpesvirus-3 annotated genes.

    Science.gov (United States)

    Ilouze, Maya; Dishon, Arnon; Kotler, Moshe

    2012-10-01

    Cyprinid herpesvirus-3 (CyHV-3) is the cause of a fatal disease in carp and koi fish. The disease is seasonal and appears when water temperatures range from 18 to 28°C. CyHV-3 is a member of the Alloherpesviridae, a family in the Herpesvirales order that encompasses mammalian, avian and reptilian viruses. CyHV-3 is a large double-stranded DNA (dsDNA) herpesvirus with a genome of approximately 295kbp, divergent from other mammalian, avian and reptilian herpesviruses, but bearing several genes similar to cyprinid herpesvirus-1 (CyHV-1), CyHV-2, anguillid herpesvirus-1 (AngHV-1), ictalurid herpesvirus-1 (IcHV-1) and ranid herpes virus-1 (RaHV-1). Here we show that viral DNA synthesis commences 4-8h post-infection (p.i.), and is completely inhibited by pre-treatment with cytosine β-d-arabinofuranoside (Ara-C). Transcription of CyHV-3 genes initiates after infection as early as 1-2h p.i., and precedes viral DNA synthesis. All 156 annotated open reading frames (ORFs) of the CyHV-3 genome are transcribed into RNAs, most of which can be classified into immediate early (IE or α), early (E or β) and late (L or γ) classes, similar to all other herpesviruses. Several ORFs belonging to these groups are clustered along the viral genome. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Anti-herpesvirus agents: a patent and literature review (2003 to present).

    Science.gov (United States)

    Skoreński, Marcin; Sieńczyk, Marcin

    2014-08-01

    The standard therapy used to treat herpesvirus infections is based on the application of DNA polymerase inhibitors such as ganciclovir or aciclovir. Unfortunately, all of these compounds exhibit relatively high toxicity and the mutation of herpesviruses results in the appearance of new drug-resistant strains. Consequently, there is a great need for the development of new, effective and safe anti-herpesvirus agents that employ different patterns of therapeutic action at various stages of the virus life cycle. Patents and patent applications concerning the development of anti-herpesvirus agents displaying different mechanisms of action that have been published since 2003 are reviewed. In addition, major discoveries in this field that have been published in academic papers have also been included. Among all the anti-herpesvirus agents described in this article, the inhibitors of viral serine protease seem to present one of the most effective/promising therapeutics. Unfortunately, the practical application of these antiviral agents has not yet been proven in any clinical trials. Nevertheless, the dynamic and extensive work on this subject gives hope that a new class of anti-herpesvirus agents aimed at the enzymatic activity of herpesvirus serine protease may be developed.

  16. Delta-9 tetrahydrocannabinol (THC inhibits lytic replication of gamma oncogenic herpesviruses in vitro

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    Friedman Herman

    2004-09-01

    Full Text Available Abstract Background The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC, has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Methods Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV and Epstein-Barr virus (EBV replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS of monkeys, murine gamma herpesvirus 68 (MHV 68, and herpes simplex type 1 (HSV-1 was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Results Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. Conclusions THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC

  17. Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

    Science.gov (United States)

    Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

    2004-09-15

    The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development

  18. Use of whole genome deep sequencing to define emerging minority variants in virus envelope genes in herpesvirus treated with novel antimicrobial K21.

    Science.gov (United States)

    Tweedy, Joshua G; Prusty, Bhupesh K; Gompels, Ursula A

    2017-10-01

    New antivirals are required to prevent rising antimicrobial resistance from replication inhibitors. The aim of this study was to analyse the range of emerging mutations in herpesvirus by whole genome deep sequencing. We tested human herpesvirus 6 treatment with novel antiviral K21, where evidence indicated distinct effects on virus envelope proteins. We treated BACmid cloned virus in order to analyse mechanisms and candidate targets for resistance. Illumina based next generation sequencing technology enabled analyses of mutations in 85 genes to depths of 10,000 per base detecting low prevalent minority variants (<1%). After four passages in tissue culture the untreated virus accumulated mutations in infected cells giving an emerging mixed population (45-73%) of non-synonymous SNPs in six genes including two envelope glycoproteins. Strikingly, treatment with K21 did not accumulate the passage mutations; instead a high frequency mutation was selected in envelope protein gQ2, part of the gH/gL complex essential for herpesvirus infection. This introduced a stop codon encoding a truncation mutation previously observed in increased virion production. There was reduced detection of the glycoprotein complex in infected cells. This supports a novel pathway for K21 targeting virion envelopes distinct from replication inhibition. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Respiratory herpesvirus infection in two Indian Ringneck parakeets.

    Science.gov (United States)

    Lazic, Tatjana; Ackermann, Mark R; Drahos, Jo M; Stasko, Judith; Haynes, Joseph S

    2008-03-01

    A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.

  20. Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-δ Syndrome

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    Jeffrey I. Cohen

    2018-02-01

    Full Text Available The phosphatidylinositol-3-kinase (PI3K/Akt pathway is important for multiple stages of herpesvirus replication including virus entry, replication, latency, and reactivation. Recently, patients with gain-of-function mutations in the p110δ-catalytic subunit of PI3K or in the p85-regulatory subunit of PI3K have been reported. These patients have constitutively active PI3K with hyperactivation of Akt. They present with lymphoproliferation and often have infections, particularly recurrent respiratory infections and/or severe virus infections. The most frequent virus infections are due to Epstein–Barr virus (EBV and cytomegalovirus (CMV; patients often present with persistent EBV and/or CMV viremia, EBV lymphoproliferative disease, or CMV lymphadenitis. No patients have been reported with CMV pneumonia, colitis, or retinitis. Other herpesvirus infections have included herpes simplex pneumonia, recurrent zoster, and varicella after vaccination with the varicella vaccine. Additional viral infections have included adenovirus viremia, severe warts, and extensive Molluscum contagiosum virus infection. The increased susceptibility to virus infections in these patients is likely due to a reduced number of long-lived memory CD8 T cells and an increased number of terminally differentiated effector CD8 T cells.

  1. The haemagglutination activity of equine herpesvirus type 1 glycoprotein C.

    Science.gov (United States)

    Andoh, Kiyohiko; Hattori, Shiho; Mahmoud, Hassan Y A H; Takasugi, Maaya; Shimoda, Hiroshi; Bannai, Hiroshi; Tsujimura, Koji; Matsumura, Tomio; Kondo, Takashi; Kirisawa, Rikio; Mochizuki, Masami; Maeda, Ken

    2015-01-02

    Equine herpesvirus type 1 (EHV-1) has haemagglutination (HA) activity toward equine red blood cells (RBCs), but the identity of its haemagglutinin is unknown. To identify the haemagglutinin of EHV-1, the major glycoproteins of EHV-1 were expressed in 293T cells, and the cells or cell lysates were mixed with equine RBCs. The results showed that only EHV-1 glycoprotein C (gC)-producing cells adsorbed equine RBCs, and that the lysate of EHV-1 gC-expressing cells agglutinated equine RBCs. EHV-1 lacking gC did not show HA activity. HA activity was inhibited by monoclonal antibodies (MAbs) specific for gC, but not by antibodies directed against other glycoproteins. In addition, HA activity was not inhibited by the addition of heparin. These results indicate that EHV-1 gC can bind equine RBCs irrespective of heparin, in contrast to other herpesvirus gC proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

    Science.gov (United States)

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-20

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

  3. Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

    NARCIS (Netherlands)

    Beek, Martha Trijntje van der

    2012-01-01

    The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to

  4. Enhanced resistance to herpes simplex virus type 1 infection in transgenic mice expressing a soluble form of herpesvirus entry mediator

    International Nuclear Information System (INIS)

    Ono, Etsuro; Yoshino, Saori; Amagai, Keiko; Taharaguchi, Satoshi; Kimura, Chiemi; Morimoto, Junko; Inobe, Manabu; Uenishi, Tomoko; Uede, Toshimitsu

    2004-01-01

    Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor (TNF) receptor family used as a cellular receptor by virion glycoprotein D (gD) of herpes simplex virus (HSV). Both human and mouse forms of HVEM can mediate entry of HSV-1 but have no entry activity for pseudorabies virus (PRV). To assess the antiviral potential of HVEM in vivo, three transgenic mouse lines expressing a soluble form of HVEM (HVEMIg) consisting of an extracellular domain of murine HVEM and the Fc portion of human IgG1 were generated. All of the transgenic mouse lines showed marked resistance to HSV-1 infection when the mice were challenged intraperitoneally with HSV-1, but not to PRV infection. The present results demonstrate that HVEMIg is able to exert a significant antiviral effect against HSV-1 infection in vivo

  5. First identification of Herpesvirus infections among endemic and exotic psittacines in Mexico

    OpenAIRE

    Turral Ramírez, Ma. Montserrat; Córdova Ponce, Rodolfo; González Ruíz, Cynthia; Castañeda Aceves, Graciela; Marín Flamand, Ernesto; Garrido Fariña, Germán; Ramírez Álvarez, Hugo

    2017-01-01

    Abstract: The illegal trafficking of exotic birds such as parrots is now the third most lucrative business in the world and has been a problem for several years. As a result of this trafficking, there has been an increase in the emergence of exotic diseases. Herpesvirus is a pathogen of psittacines that has not been identified in Mexico to date. Through the use of polymerase chain reaction (PCR) assays and pathological analyses, the present study demonstrates the presence of herpesvirus in en...

  6. Herpesvirus in a captive Australian Krefft's river turtle (Emydura macquarii krefftii).

    Science.gov (United States)

    Cowan, M L; Raidal, S R; Peters, A

    2015-01-01

    A mature, captive Krefft's river turtle (Emydura macquarii krefftii) was presented with severe proliferative and ulcerative lesions of the skin and shell. The areas were biopsied and histopathological examination demonstrated orthokeratotic hyperkeratosis with keratinocytes containing eosinophilic intranuclear inclusions. Molecular diagnostics confirmed the presence of a herpesvirus in the affected tissues. This is the first recorded case of herpesvirus infection in an Australian freshwater turtle species. © 2015 Australian Veterinary Association.

  7. Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Wu, Meiqing; Huang, Fen; Jiang, Xinmiao; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Jiang, Qianli; Zhang, Yu; Zhao, Ke; Xuan, Li; Zhai, Xiao; Zhang, Fuhua; Yin, Changxin; Sun, Jing; Feng, Ru; Liu, Qifa

    2013-01-01

    Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)-associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD) was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

  8. Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to "Megavirales".

    Science.gov (United States)

    Mushegian, Arcady; Karin, Eli Levy; Pupko, Tal

    2018-01-01

    The order Herpesvirales includes animal viruses with large double-strand DNA genomes replicating in the nucleus. The main capsid protein in the best-studied family Herpesviridae contains a domain with HK97-like fold related to bacteriophage head proteins, and several virion maturation factors are also homologous between phages and herpesviruses. The origin of herpesvirus DNA replication proteins is less well understood. While analyzing the genomes of herpesviruses in the family Malacohepresviridae, we identified nearly 30 families of proteins conserved in other herpesviruses, including several phage-related domains in morphogenetic proteins. Herpesvirus DNA replication factors have complex evolutionary history: some are related to cellular proteins, but others are closer to homologs from large nucleocytoplasmic DNA viruses. Phylogenetic analyses suggest that the core replication machinery of herpesviruses may have been recruited from the same pool as in the case of other large DNA viruses of eukaryotes. Published by Elsevier Inc.

  9. Identification of a novel herpesvirus associated with a penile proliferative lesion in a beluga (Delphinapterus leucas).

    Science.gov (United States)

    Bellehumeur, Christian; Lair, Stéphane; Romero, Carlos H; Provost, Chantale; Nielsen, Ole; Gagnon, Carl A

    2015-01-01

    The carcass of an adult male beluga (Delphinapterus leucas) was found beach cast in 2008 on the shore of the St. Lawrence Estuary at Rivière-Ouelle, Quebec, Canada. The carcass was transported to the Faculté de médecine vétérinaire of the Université de Montréal for postmortem examination. Aspiration pneumonia was the probable cause of death. Necropsy revealed a focal papilloma-like penile lesion, characterized by focal mucosal thickening with disorganization of the epithelial layers and lymphoplasmacytic infiltration. A pan-herpesvirus nested PCR assay on frozen tissue from the penile lesion was positive. The PCR product sequencing revealed a partial herpesvirus DNA polymerase (DPOL) gene sequence of 600 nucleotides. Its nearest nucleotide identity was with the partial DPOL gene of an alphaherpesvirus, bovine herpesvirus 5 (79.5% identity). It also shared high identity with several other marine mammal herpesviruses (50.2 to 77.3% identity). This new herpesvirus was tentatively named beluga whale herpesvirus (BWHV). Virus isolation was unsuccessful. The pathogenic potential of BWHV is unknown, but the evaluation of archived tissues suggests that the virus is endemic in the St. Lawrence Estuary beluga population.

  10. Ranid Herpesvirus 3 and Proliferative Dermatitis in Free-Ranging Wild Common Frogs (Rana Temporaria).

    Science.gov (United States)

    Origgi, F C; Schmidt, B R; Lohmann, P; Otten, P; Akdesir, E; Gaschen, V; Aguilar-Bultet, L; Wahli, T; Sattler, U; Stoffel, M H

    2017-07-01

    Amphibian pathogens are of current interest as contributors to the global decline of amphibians. However, compared with chytrid fungi and ranaviruses, herpesviruses have received relatively little attention. Two ranid herpesviruses have been described: namely, Ranid herpesvirus 1 (RHV1) and Ranid herpesvirus 2 (RHV2). This article describes the discovery and partial characterization of a novel virus tentatively named Ranid herpesvirus 3 (RHV3), a candidate member of the genus Batrachovirus in the family Alloherpesviridae. RHV3 infection in wild common frogs (Rana temporaria) was associated with severe multifocal epidermal hyperplasia, dermal edema, a minor inflammatory response, and variable mucous gland degeneration. Intranuclear inclusions were numerous in the affected epidermis together with unique extracellular aggregates of herpesvirus-like particles. The RHV3-associated skin disease has features similar to those of a condition recognized in European frogs for the last 20 years and whose cause has remained elusive. The genome of RHV3 shares most of the features of the Alloherpesviruses. The characterization of this presumptive pathogen may be of value for amphibian conservation and for a better understanding of the biology of Alloherpesviruses.

  11. Epidemiology, disease and control of infections in ruminants by herpesviruses - an overview : review article

    Directory of Open Access Journals (Sweden)

    J.R. Patel

    2008-05-01

    Full Text Available There are at least 16 recognised herpesviruses that naturally infect cattle, sheep, goats and various species of deer and antelopes. Six of the viruses are recognised as distinct alphaherpesviruses and 9 as gammaherpesviruses. Buffalo herpesvirus (BflHV and ovine herpesvirus-1 (OvHV-1 remain officially unclassified. The prevalence of ruminant herpesviruses varies from worldwide to geographically restricted in distribution. Viruses in both subfamilies Alphaherpesvirinae and Gammaherpesvirinae cause mild to moderate and severe disease in respective natural or secondary ruminant hosts. Accordingly, the economic and ecological impact of the viruses is also variable. The molecular characteristics of some members have been investigated in detail. This has led to the identification of virulence-associated genes and construction of deletion mutants and recombinant viruses. Some of the latter have been developed as commercial vaccines. This paper aims to give an overview of the epidemiology and pathogenesis of infection by these viruses, immuno-prophylaxis and mechanisms of recovery from infection. Since there are 128 ruminant species in the family Bovidae, it is likely that some herpesviruses remain undiscovered. We conclude that currently known ruminant alphaherpesviruses occur only in their natural hosts and do not cross stably into other ruminant species. By contrast, gammaherpesviruses have a much broader host range as evidenced by the fact that antibodies reactive to alcelaphine herpesvirus type 1 have been detected in 4 subfamilies in the family Bovidae, namely Alcelaphinae, Hippotraginae, Ovibovinae and Caprinae. New gammaherpesviruses within these subfamilies are likely to be discovered in the future.

  12. Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

    Directory of Open Access Journals (Sweden)

    Fengchun Ye

    2011-01-01

    Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

  13. Esophagitis and enteritis caused by herpesvirus in pigeons.

    Directory of Open Access Journals (Sweden)

    Egobol, L.

    2002-01-01

    Full Text Available The pigeon squabs, aged 5-26 day-old, showed clinical signs of dullness, anorexia, indigestion, reten-tion of feed in crop, progressive emaciation then died. The morbidity rate and mortality rate were 7.14% (50/700. The adult pigeons did not show any signs of disease. From pathological finding, pharyngitis, esophagitis were found with diphtheritic membrane covering necrotic ulcers on the mucosa of pharynx, esophagus and crop. From histopathological findings, esophagitis with epithelial hyperplasia and sloughed, lamina propria mucosa edema with lymphoid cells infiltration were found in duodenum and jejunum. The intranuclear inclusion body, Cowdry type A, was found in epithelial mucosa of esophagus, enterocyte of jejunum and lymphoid cells in spleen. FA test to duck virus enteritis and inoculation to ducklings showed negative results. Electron microscopic study revealed electron dense core sized 146-167 nm., which was identified as herpesvirus.

  14. Major immunogenic proteins of phocid herpes-viruses and their relationships to proteins of canine and feline herpesviruses.

    Science.gov (United States)

    Harder, T C; Harder, M; de Swart, R L; Osterhaus, A D; Liess, B

    1998-04-01

    The immunogenic proteins of cells infected with the alpha- or the gamma-herpesvirus of seals, phocid herpesvirus-1 and -2 (PhHV-1, -2), were examined in radioimmunoprecipitation assays as a further step towards the development of a PhHV-1 vaccine. With sera obtained from convalescent seals of different species or murine monoclonal antibodies (Mabs), at least seven virus-induced glycoproteins were detected in lysates of PhHV-1-infected CrFK cells. A presumably disulphide-linked complex composed of glycoproteins of 59, 67 and 113/120 kDa, expressed on the surface of infected cells, was characterized as a major immunogenic infected cell protein of PhHV-1. This glycoprotein complex has previously been identified as the proteolytically cleavable glycoprotein B homologue of PhHV-1 (14). At least three distinct neutralization-relevant epitopes were operationally mapped, by using Mabs, on the glycoprotein B of PhHV-1. Among the infected cell proteins of the antigenically closely related feline and canine herpesvirus, the glycoprotein B equivalent proved to be the most highly conserved glycoprotein. Sera obtained from different seal species from Arctic, Antarctic, and European habitats did not precipitate uniform patterns of infected cell proteins from PhHV-1-infected cell lysates although similar titres of neutralizing antibodies were displayed. Thus, antigenic differences among the alphaherpesvirus species prevalent in the different pinniped populations cannot be excluded. PhHV-2 displayed a different pattern of infected cell proteins and only limited cross-reactivity to PhHV-1 at the protein level was detected, which is in line with its previous classification as a distinct species, based on nucleotide sequence analysis, of the gammaherpesvirus linenge. A Mab raised against PhHV-2 and specific for a major glycoprotein of 117 kDa, cross reacted with the glycoprotein B of PhHV-1. The 117-kDa glycoprotein could represent the uncleaved PhHV-2 glycoprotein B homologue.

  15. Coagulation parameters following equine herpesvirus type 1 infection in horses.

    Science.gov (United States)

    Wilson, M E; Holz, C L; Kopec, A K; Dau, J J; Luyendyk, J P; Soboll Hussey, G

    2018-04-15

    Equine herpesvirus type 1 (EHV-1) is the cause of respiratory disease, abortion storms, and outbreaks of herpesvirus myeloencephalopathy (EHM). Infection of the spinal cord is characterised by multifocal regions of virally infected vascular endothelium, associated with vasculitis, thrombosis and haemorrhage that result in ischaemia and organ dysfunction. However, the mechanism of thrombosis in affected horses is unknown. To evaluate tissue factor (TF) procoagulant activity and thrombin-antithrombin complex (TAT) levels in horses following infection with EHV-1. In vitro and in vivo studies following experimental EHV-1 infection. Horses were infected with EHV-1 and levels of peripheral blood mononuclear cell (PBMC)-associated TF activity; plasma and cerebrospinal fluid (CSF)-derived microvesicle (MV)-associated TF activity and TAT complexes in plasma were examined. EHV-1 infection increased PBMC TF procoagulant activity in vitro and in vivo. In infected horses, this increase was observed during the acute infection and was most marked at the onset and end of viraemia. However, no significant differences were observed between the horses that showed signs of EHM and the horses that did not develop EHM. Significant changes in MV-associated TF procoagulant activity and TAT complexes were not observed in infected horses. A small number of horses typically exhibit clinical EHM following experimental infection. The results indicate that EHV-1 infection increases PBMC-associated TF procoagulant activity in vivo and in vitro. Additional in vivo studies are needed to better understand the role of TF-dependent coagulation during EHM pathogenesis in horses. © 2018 EVJ Ltd.

  16. Envelope proteins of bovine herpesvirus 1: immunological and biochemical studies

    International Nuclear Information System (INIS)

    Rodriguez Roque, L.L.

    1986-01-01

    The authors studied immunological and biochemical properties of the bovid herpesvirus 1 (BHV-1) envelope proteins in order to understand the pathogenesis of BHV-1 infection and to provide basic information for the production of effective subunit vaccines against BHV-1. Ten glycoproteins MW 180, 150, 130, 115, 97, 77, 74, 64, 55, and 45 kilodaltons (K), and a single non-glycosylated 108 K protein were quantitatively removed from purified BHV-1 virions by detergent treatment. These glycoproteins were present on the virion envelope and on the surface of BHV-1 infected cells. The quantitative removal from virions by treatment with nonionic detergents and their presence on the surface of infected cells indicate that 180/97, 150/77, and 130/74/55 K are major components of the BHV-1 envelope and are also the targets of virus neutralizing humoral immune response. Envelope glycoproteins of herpes simplex type 1 (HSV-1) bind immunoglobulin by the Fc end and it is suggested this may increase pathogenicity of this virus. They searched for a similar function in BVH-1 by measuring the ability of BHV-1 infected cells and viral envelope proteins to bind radiolabelled rabbit and bovine IgG. Binding activity for rabbit IgG or bovine IgG-Fc could not be demonstrated by BHV-1 infected MDBK cells, whereas, MDBK cells infected with HSV-1 bound rabbit IgG and bovine IgG-Fc. None of the three major envelope proteins of BHV-1 bound to rabbit or bovine IgG. The results of this study indicate that BHV-1, unlike some other herpesviruses, lack Fc binding activity

  17. The development of a loop-mediated isothermal amplification assay for rapid and sensitive detection of abalone herpesvirus DNA.

    Science.gov (United States)

    Chen, M H; Kuo, S T; Renault, T; Chang, P H

    2014-02-01

    A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of abalone herpesvirus DNA. Two pairs of primers were designed, based on the sequence of the DNA polymerase gene of abalone herpesvirus. The reaction temperature and time were optimized to 63°C and 60min, respectively. LAMP amplicons were analyzed by 2% agarose gel electrophoresis or by visual inspection of a colour change emitted by fluorescent dye. The method developed was specific for the detection of abalone herpesvirus, without cross-reactions with other tested herpesviruses including ostreid herpesvirus 1 (OsHV-1), European eel herpesvirus, koi herpesvirus (KHV) and an avian herpesvirus. The LAMP assay was 100 folds more sensitive than a conventional PCR and 10 folds less sensitive than a SYBR Green PCR. These results indicate that the developed LAMP assay is a simple, rapid, sensitive, specific and reliable technique for the detection of abalone herpesvirus. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Protein complexes associated with the Kaposi's sarcoma-associated herpesvirus-encoded LANA

    International Nuclear Information System (INIS)

    Kaul, Rajeev; Verma, Subhash C.; Robertson, Erle S.

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA is known to modulate viral and cellular gene expression. We report here on some initial proteomic studies to identify cellular proteins associated with the amino and carboxy-terminal domains of LANA. The results of these studies show an association of known cellular proteins which support LANA functions and have identified additional LANA-associated proteins. These results provide new evidence for complexes involving LANA with a number of previously unreported functional classes of proteins including DNA polymerase, RNA helicase and cell cycle control proteins. The results also indicate that the amino terminus of LANA can interact with its carboxy-terminal domain. This interaction is potentially important for facilitating associations with other cell cycle regulatory proteins which include CENP-F identified in association with both the amino and carboxy-termini. These novel associations add to the diversity of LANA functions in relation to the maintenance of latency and subsequent transformation of KSHV infected cells

  19. The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study

    Science.gov (United States)

    Ling, Paul D.; Lednicky, John A.; Keitel, Wendy A.; Poston, David G.; White, Zoe S.; Peng, RongSheng; Liu, Zhensheng; Mehta, Satish K.; Pierson, Duane L.; Rooney, Cliona M.; hide

    2003-01-01

    Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (Por=40 years old (P.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

  20. Replacement of glycoprotein B in alcelaphine herpesvirus 1 by its ovine herpesvirus 2 homolog: Implications in vaccine development for sheep-associated malignant catarrhal fever

    Science.gov (United States)

    Vaccine development is a top priority in malignant catarrhal fever (MCF) research. In the case of sheep-associated MCF (SA-MCF), caused by ovine herpesvirus 2 (OvHV-2), progress towards this objective has been hindered by the absence of methods to attenuate or modify the virus, since it cannot be pr...

  1. In Vitro Replication of Chelonid Herpesvirus 5 in Organotypic Skin Cultures from Hawaiian Green Turtles (Chelonia mydas).

    Science.gov (United States)

    Work, Thierry M; Dagenais, Julie; Weatherby, Tina M; Balazs, George H; Ackermann, Mathias

    2017-09-01

    Fibropapillomatosis (FP) is a tumor disease of marine turtles associated with chelonid herpesvirus 5 (ChHV5), which has historically been refractory to growth in tissue culture. Here we show, for the first time, de novo formation of ChHV5-positive intranuclear inclusions in cultured green turtle cells, which is indicative of active lytic replication of the virus. The minimal requirements to achieve lytic replication in cultured cells included (i) either in vitro cultures of ChHV5-positive tumor biopsy specimens (plugs) or organotypic cultures (rafts) consisting of ChHV5-positive turtle fibroblasts in collagen rafts seeded with turtle keratinocytes and (ii) keratinocyte maturation induced by raising raft or biopsy cultures to the air-liquid interface. Virus growth was confirmed by detailed electron microscopic studies that revealed intranuclear sun-shaped capsid factories, tubules, various stages of capsid formation, nuclear export by budding into the perinuclear space, tegument formation, and envelopment to complete de novo virus production. Membrane synthesis was also observed as a sign of active viral replication. Interestingly, cytoplasmic particles became associated with keratin filaments, a feature not seen in conventional monolayer cell cultures, in which most studies of herpesvirus replication have been performed. Our findings draw a rich and realistic picture of ChHV5 replication in cells derived from its natural host and may be crucial not only to better understand ChHV5 circulation but also to eventually complete Koch's postulates for FP. Moreover, the principles described here may serve as a model for culture of other viruses that are resistant to replication in conventional cell culture. IMPORTANCE A major challenge in virology is the study of viruses that cannot be grown in the laboratory. One example is chelonid herpesvirus 5 (ChHV5), which is associated with fibropapillomatosis, a globally distributed, debilitating, and fatal tumor disease of

  2. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

    Science.gov (United States)

    Diner, Benjamin A; Lum, Krystal K; Toettcher, Jared E; Cristea, Ileana M

    2016-11-15

    The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. How mammalian cells detect and respond to DNA viruses that replicate in the nucleus is poorly understood. Here, we decipher the distinct functions of two viral DNA sensors, IFI16 and cGAS, during active immune signaling upon infection with two herpesviruses, herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV). We show that IFI16

  3. Epidemiology and molecular detection of equine herpesviruses in western Algeria in 2011.

    Science.gov (United States)

    Laabassi, F; Hue, E; Fortier, C; Morilland, E; Legrand, L; Hans, A; Pronost, S

    2017-08-01

    An episode of acute equine respiratory infection was reported in western Algeria (Tiaret province) between February and March 2011, affecting a large population of horses. Nasal swabs (n=100) were taken from horses aged between 1 and 27 years, presenting with cough and mucopurulent nasal discharge. The prevalence of equine respiratory virus infections was examined using quantitative polymerase chain reaction (qPCR). One, or more, of four equine respiratory viruses were detected in the nasal swabs of 90 of 100 horses (90%) and the detection rate of equine herpesvirus type 1 (EHV-1), equine herpesvirus type 4 (EHV-4), equine herpesvirus type 2 (EHV-2) and equine herpesvirus type 5 (EHV-5) were 2%, 14%, 90% and 75%, respectively. Equine influenza virus and equine arteritis virus were not detected in any samples. Among the 90 infected horses, 70 were co-infected with EHV-2 and EHV-5 and 14 others were co-infected with EHV-4, EHV-2 and EHV-5. The present study shows a positivity rate of 97.3% for EHV-5 in young horses aged equine herpesviruses 1, 2, 4 and 5 are endemic in horse populations from Algeria as detected for the first time by qPCR. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Genotypic characterization of psittacid herpesvirus isolates from Brazil.

    Science.gov (United States)

    Luppi, Marcela Miranda; Luiz, Ana Paula Moreira Franco; Coelho, Fabiana Magalhães; Ecco, Roselene; da Fonseca, Flávio Guimarães; Resende, Mauricio

    2016-01-01

    Thirty-six isolates of psittacid herpesvirus (PsHV), obtained from 12 different species of psittacids in Brazil, were genotypically characterized by restriction fragment length polymorphism (RFLP) analysis and PCR amplification. RFLP analysis with the PstI enzyme revealed four distinct restriction patterns (A1, X, W and Y), of which only A1 (corresponding to PsHV-1) had previously been described. To study PCR amplification patterns, six pairs of primers were used. Using this method, six variants were identified, of which, variants 10, 8, and 9 (in this order) were most prevalent, followed by variants 1, 4, and 5. It was not possible to correlate the PCR and RFLP patterns. Twenty-nine of the 36 isolates were shown to contain a 419bp fragment of the UL16 gene, displaying high similarity to the PsHV-1 sequences available in GenBank. Comparison of the results with the literature data suggests that the 36 Brazilian isolates from this study belong to genotype 1 and serotype 1. Copyright © 2015 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  5. Nationwide Cyprinid herpesvirus 3 contamination in natural rivers of Japan.

    Science.gov (United States)

    Minamoto, Toshifumi; Honjo, Mie N; Yamanaka, Hiroki; Uchii, Kimiko; Kawabata, Zen'ichiro

    2012-08-01

    Cyprinid herpesvirus 3 (CyHV-3) disease is a significant threat for common and koi carp cultivators and for freshwater ecosystems. To determine the prevalence of CyHV-3 in Japanese rivers, a nationwide survey of all national class-A rivers was undertaken in the Summer of 2008. The virus was concentrated from river water samples using the cation-coated filter method. CyHV-3 DNA was detected in 90 rivers, representing 90% of 103 successfully analysed rivers. More than 100,000 copies of CyHV-3 DNA per litre of sample were detected in four rivers, higher than that reported during the Yura River outbreak in 2007. For CyHV-3-positive rivers, the log CyHV-3 density was negatively correlated with the water temperature on the sampling date and positively correlated with the suspended solids and dissolved oxygen, which are annually averaged for each river. Our results demonstrate that virus detection using molecular biology techniques is a powerful tool for monitoring the presence of CyHV-3 in natural environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

    Energy Technology Data Exchange (ETDEWEB)

    Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.; (UPENN)

    2009-12-01

    Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.

  7. Columbid herpesvirus-1 in two Cooper's hawks (Accipiter cooperii) with fatal inclusion body disease.

    Science.gov (United States)

    Pinkerton, Marie E; Wellehan, James F X; Johnson, April J; Childress, April L; Fitzgerald, Scott D; Kinsel, Michael J

    2008-07-01

    We report two separate naturally occurring cases of fatal herpesviral disease in Cooper's Hawks (Accipiter cooperii). Gross lesions included splenomegaly and hepatomegaly, with diffuse pale mottling or scattered small white foci. Histologic lesions included splenic and hepatic necrosis associated with eosinophilic intranuclear inclusion bodies characteristic of herpesvirus. In one case, necrosis and inclusions were also noted in bone marrow, thymus, bursa of Fabricius, thyroid gland, parathyroid gland, ceca, and the enteric system. Transmission electron microscopy demonstrated viral particles typical of herpesvirus within hepatocyte nuclei and budding from the nuclear membrane. Herpesviral DNA was amplified via polymerase chain reaction (PCR) of paraffin-embedded liver and spleen, and sequence data were consistent with columbid herpesvirus-1, an alphaherpesvirus of Rock Pigeons (Columba livia). PCR results provide evidence that this disease is transmitted to raptors via Rock Pigeons, most likely through ingestion of Rock Pigeons as prey.

  8. Prevalence of asinine herpesvirus type 5 (AsHV-5) infection in clinically normal Lipizzaner horses.

    Science.gov (United States)

    Rushton, James Oliver; Kolodziejek, Jolanta; Nell, Barbara; Nowotny, Norbert

    2014-04-01

    The aim of this study was to assess the extent of asinine herpesvirus (AsHV) type 5 infection in 'closed' populations of clinically normal Lipizzaner horses. Peripheral blood mononuclear cells plus nasal and conjunctival swabs were obtained on four occasions over an 18 month period from 266 animals as part of a health surveillance programme. Sequence analysis of samples that were positive by nested consensus herpesvirus PCR but negative using quantified equid herpesvirus (EHV) type 2 and 5 PCR, revealed a total of 51 samples from 39 horses positive for AsHV-5. No statistically significant association between animal age, gender or geographical location and infection status was identified. The findings suggest sub-clinical AsHV-5 infection may be encountered more frequently than previously reported. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Current status of herpesvirus identification in the oral cavity of HIV-infected children

    Directory of Open Access Journals (Sweden)

    Raquel dos Santos Pinheiro

    2013-01-01

    Full Text Available INTRODUCTION: Some viruses of the Herpesviridae family are frequently the etiologic agents of oral lesions associated with HIV. The aim of this study was to identify the presence of herpes simplex virus types 1 and 2 (HSV-1, HSV-2, Varicella Zoster virus (VZV, Epstein-Barr virus (EBV, human cytomegalovirus (HCMV, human herpesvirus type 6, type 7 and type 8 (HHV-6, HHV-7 and HHV-8 in the oral cavity of HIV-infected children/adolescents and verify the association between viral subtypes and clinical factors. METHODS: The cells of oral mucosa were collected from 50 HIV infected children/adolescents, 3-13 years old (mean age 8.66. The majority (66% of selected were girls, and they were all outpatients at the pediatric AIDS clinic of a public hospital in Rio de Janeiro. Nested-PCR was used to identify the viral types. RESULTS: Absence of immunosuppression was observed in 66% of the children. Highly active antiretroviral therapy (HAART was used by 72.1% of selected and moderate viral load was observed in 56% of the children/adolescents. Viral types were found in 86% of the children and the subtypes were: HSV-1 (4%, HSV-2 (2%, VZV (4%, EBV (0%, HCMV (24%, HHV6 (18%, HHV-7 (68%, HHV8 (0%. CONCLUSIONS: The use of HAART has helped to reduce oral lesions, especially with herpes virus infections. The health professionals who work with these patients should be aware of such lesions because of their predictive value and the herpes virus can be found circulating in the oral cavity without causing lesions.

  10. Herpesvirus of turkeys: microarray analysis of host gene responses to infection

    International Nuclear Information System (INIS)

    Karaca, Gamze; Anobile, Jonathan; Downs, Danielle; Burnside, Joan; Schmidt, Carl J.

    2004-01-01

    Herpesvirus of turkeys (HVT) provides an economically important live vaccine for prevention of Marek's disease (MD) of chickens. MD, characterized by both immunosuppression and T-cell lymphoma, is caused by another herpesvirus termed Marek's disease virus (MDV). Microarrays were used to investigate the response of chicken embryonic fibroblasts (CEF) to infection with HVT. Genes responding to HVT infection include several induced by interferon along with others modulating signal transduction, transcription, scaffolding proteins, and the cytoskeleton. Results are compared with earlier studies examining the responses of CEF cells to infection with MDV

  11. Global distribution of Chelonid fibropapilloma-associated herpesvirus among clinically healthy sea turtles

    DEFF Research Database (Denmark)

    Alfaro Nuñez, Luis Alonso; Bertelsen, Mads Frost; Bojesen, Anders Miki

    2014-01-01

    BackgroundFibropapillomatosis (FP) is a neoplastic disease characterized by cutaneous tumours that has been documented to infect all sea turtle species. Chelonid fibropapilloma-associated herpesvirus (CFPHV) is believed to be the aetiological agent of FP, based principally on consistent PCR......-based detection of herpesvirus DNA sequences from FP tumours. We used a recently described PCR-based assay that targets 3 conserved CFPHV genes, to survey 208 green turtles (Chelonia mydas). This included both FP tumour exhibiting and clinically healthy individuals. An additional 129 globally distributed...

  12. Molecular characterization of Marek's disease herpesvirus B antigen

    International Nuclear Information System (INIS)

    Isfort, R.J.; Sithole, I.; Kung, H.J.; Velicer, L.F.

    1986-01-01

    The Marek's disease herpesvirus (MDHV) B antigen (MDHV-B) was identified and molecularly characterized as a set of three glycoproteins of 100,000, 60,000, and 49,000 apparent molecular weight (gp100, gp60, and gp49, respectively) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after immunoprecipitation from [ 35 S]methionine-labeled infected cells by specific rabbit antiserum directed against MDHV-B (RαB), as previously determined by immunodiffusion. Further identification was accomplished by blocking this immunoprecipitation with highly purified MDHV-B. The same set of three polypeptides was also immunoprecipitated from [ 35 S] methionine- and 14 C-labeled infected cells into two other sera shown to have anti-B activity. These data serve to clarify the molecular identification of the polypeptides found in common between MDHV and HVT by linking them to MDHV-B. Collectively, the data presented here and by others support the conclusion that all three glycoproteins now identified as gp100, gp60, and gp49 have MDHV-B determinants. Finally, detection of the same three polypeptides with well-absorbed RαPM, which was directed against purified infected-cell plasma membranes, suggests that at least one component of the B-antigen complex has a plasma membrane location in the infected cell. These preliminary data point to the future membrane biochemistry and membrane immunology experiments needed to understand the MDHV system, and they may explain the high level of immunogenicity of MDHV-B in the infected chicken, as shown by its immunoprecipitation with immune chicken serum

  13. Linkage map of the fragments of herpesvirus papio DNA.

    Science.gov (United States)

    Lee, Y S; Tanaka, A; Lau, R Y; Nonoyama, M; Rabin, H

    1981-01-01

    Herpesvirus papio (HVP), an Epstein-Barr-like virus, causes lymphoblastoid disease in baboons. The physical map of HVP DNA was constructed for the fragments produced by cleavage of HVP DNA with restriction endonucleases EcoRI, HindIII, SalI, and PvuI, which produced 12, 12, 10, and 4 fragments, respectively. The total molecular size of HVP DNA was calculated as close to 110 megadaltons. The following methods were used for construction of the map; (i) fragments near the ends of HVP DNA were identified by treating viral DNA with lambda exonuclease before restriction enzyme digestion; (ii) fragments containing nucleotide sequences in common with fragments from the second enzyme digest of HVP DNA were examined by Southern blot hybridization; and (iii) the location of some fragments was determined by isolating individual fragments from agarose gels and redigesting the isolated fragments with a second restriction enzyme. Terminal heterogeneity and internal repeats were found to be unique features of HVP DNA molecule. One to five repeats of 0.8 megadaltons were found at both terminal ends. Although the repeats of both ends shared a certain degree of homology, it was not determined whether they were identical repeats. The internal repeat sequence of HVP DNA was found in the EcoRI-C region, which extended from 8.4 to 23 megadaltons from the left end of the molecule. The average number of the repeats was calculated to be seven, and the molecular size was determined to be 1.8 megadaltons. Similar unique features have been reported in EBV DNA (D. Given and E. Kieff, J. Virol. 28:524-542, 1978). Images PMID:6261015

  14. Identification of an essential virulence gene of cyprinid herpesvirus 3.

    Science.gov (United States)

    Boutier, Maxime; Gao, Yuan; Vancsok, Catherine; Suárez, Nicolás M; Davison, Andrew J; Vanderplasschen, Alain

    2017-09-01

    The genus Cyprinivirus consists of a growing list of phylogenetically related viruses, some of which cause severe economic losses to the aquaculture industry. The archetypal member, cyprinid herpesvirus 3 (CyHV-3) causes mass mortalities worldwide in koi and common carp. A CyHV-3 mutant was described previously that is attenuated in vivo by a deletion affecting two genes (ORF56 and ORF57). The relative contributions of ORF56 and ORF57 to the safety and efficacy profile of this vaccine candidate have now been assessed by analysing viruses individually deleted for ORF56 or ORF57. Inoculation of these viruses into carp demonstrated that the absence of ORF56 did not affect virulence, whereas the absence of ORF57 led to an attenuation comparable to, though slightly less than, that of the doubly deleted virus. To demonstrate further the role of ORF57 as a key virulence factor, a mutant retaining the ORF57 region but unable to express the ORF57 protein was produced by inserting multiple in-frame stop codons into the coding region. Analysis of this virus in vivo revealed a safety and efficacy profile comparable to that of the doubly deleted virus. These findings show that ORF57 encodes an essential CyHV-3 virulence factor. They also indicate that ORF57 orthologues in other cypriniviruses may offer promising targets for the rational design of attenuated recombinant vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Geographic variation in the prevalence of Kaposi sarcoma-associated herpesvirus and risk factors for transmission.

    Science.gov (United States)

    de Sanjose, Silvia; Mbisa, Georgina; Perez-Alvarez, Susana; Benavente, Yolanda; Sukvirach, Sukhon; Hieu, Nguyen Trong; Shin, Hai-Rim; Anh, Pham Thi Hoang; Thomas, Jaiyeola; Lazcano, Eduardo; Matos, Elena; Herrero, Rolando; Muñoz, Nubia; Molano, Monica; Franceschi, Silvia; Whitby, Denise

    2009-05-15

    The aim of the present study was to estimate the prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in the female general population, to define geographic variation in and heterosexual transmission of the virus. The study included 10,963 women from 9 countries for whom information on sociodemographic characteristics and reproductive, sexual, and smoking behaviors were available. Antibodies against KSHV that encoded lytic antigen K8.1 and latent antigen ORF73 were determined. The range of prevalence of KSHV (defined as detection of any antigen) was 3.81%-46.02%, with significant geographic variation noted. In Nigeria, the prevalence was 46.02%; in Colombia, 13.32%; in Costa Rica, 9.81%; in Argentina, 6.40%; in Ho Chi Minh City, Vietnam, 15.50%; in Hanoi, Vietnam, 11.26%; in Songkla, Thailand, 10%; in Lampang, Thailand, 8.63%; in Korea, 4.93%; and in Spain, 3.65%. The prevalence of KSHV slightly increased with increasing age among subjects in geographic areas where the prevalence of KSHV was high, such as Nigeria and Colombia, and it significantly decreased with increases in the educational level attained by subjects in those areas. KSHV was not statistically associated with age at first sexual intercourse, number of sex partners, number of children, patterns of oral contraceptive use, presence of cervical human papillomavirus DNA, or smoking status. The study provides comparable estimates of KSHV prevalence in diverse cultural settings across 4 continents and provides evidence that sexual transmission of KSHV is not a major source of infection in the general population.

  16. LACK OF ASSOCIATION BETWEEN HERPESVIRUS DETECTION IN SALIVA AND GINGIVITIS IN HIV‑INFECTED CHILDREN.

    Science.gov (United States)

    Otero, Renata A; Nascimento, Flávia N N; Souza, Ivete P R; Silva, Raquel C; Lima, Rodrigo S; Robaina, Tatiana F; Câmara, Fernando P; Santos, Norma; Castro, Gloria F

    2015-01-01

    The aims of this study were to compare the detection of human herpesviruses (HHVs) in the saliva of HIV-infected and healthy control children, and to evaluate associations between viral infection and gingivitis and immunodeficiency. Saliva samples were collected from 48 HIV-infected and 48 healthy control children. Clinical and laboratory data were collected during dental visits and from medical records. A trained dentist determined gingival indices and extension of gingivitis. Saliva samples were tested for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by nested polymerase chain reaction assays. Thirty-five HIV-infected and 16 control children had gingivitis. Seventeen (35.4%) HIV-infected children and 13 (27%) control children were positive for HHVs. CMV was the most commonly detected HHV in both groups (HIV-infected, 25%; control, 12.5%), followed by HSV-1 (6.2% in both groups) and HSV-2 (HIV-infected, 4.2%; control, 8.3%). The presence of HHVs in saliva was not associated with the presence of gingivitis in HIV-1-infected children (p = 0.104) or healthy control children (p = 0.251), or with immunosuppression in HIV-infected individuals (p = 0.447). Gingivitis was correlated with HIV infection (p = 0.0001). These results suggest that asymptomatic salivary detection of HHVs is common in HIV-infected and healthy children, and that it is not associated with gingivitis.

  17. RNA epitranscriptomics: Regulation of infection of RNA and DNA viruses by N6 -methyladenosine (m6 A).

    Science.gov (United States)

    Tan, Brandon; Gao, Shou-Jiang

    2018-04-26

    N 6 -methyladenosine (m 6 A) was discovered 4 decades ago. However, the functions of m 6 A and the cellular machinery that regulates its changes have just been revealed in the last few years. m 6 A is an abundant internal mRNA modification on cellular RNA and is implicated in diverse cellular functions. Recent works have demonstrated the presence of m 6 A in the genomes of RNA viruses and transcripts of a DNA virus with either a proviral or antiviral role. Here, we first summarize what is known about the m 6 A "writers," "erasers," "readers," and "antireaders" as well as the role of m 6 A in mRNA metabolism. We then review how the replications of numerous viruses are enhanced and restricted by m 6 A with emphasis on the oncogenic DNA virus, Kaposi sarcoma-associated herpesvirus (KSHV), whose m 6 A epitranscriptome was recently mapped. In the context of KSHV, m 6 A and the reader protein YTHDF2 acts as an antiviral mechanism during viral lytic replication. During viral latency, KSHV alters m 6 A on genes that are implicated in cellular transformation and viral latency. Lastly, we discuss future studies that are important to further delineate the functions of m 6 A in KSHV latent and lytic replication and KSHV-induced oncogenesis. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Phylogenetic characterization of a novel herpesvirus found in the liver and lungs of a Chilean flamingo (Phoenicopterus chilensis).

    Science.gov (United States)

    Coverdill, Christopher C; Barnes, Julie A; Garner, Michael M; Hinton, Kevin L; Childress, April L; Wellehan, James F X

    2016-05-01

    A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in California. Postmortem examination identified a pale, enlarged liver, mildly increased fluid in the lungs, and red foci in the spleen. Histologic examination revealed marked hepatic necrosis with syncytia, splenic necrosis, and interstitial pneumonia with eosinophilic intranuclear inclusions within hepatocytes and in unidentified cells of the lung. Transmission electron microscopy identified virions consistent with a herpesvirus in the nucleus and cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus in the subfamily Alphaherpesvirinae. © 2016 The Author(s).

  19. Virulence and genotype of a bovine herpesvirus 1 isolate from semen of a subclinically infected bull

    NARCIS (Netherlands)

    Oirschot, van J.T.; Rijsewijk, F.A.M.; Straver, P.J.; Ruuls, R.C.; Quak, J.; Davidse, A.; Westenbrink, E.; Gielkens, A.L.J.; Dijk, van J.E.; Moerman, A.

    1995-01-01

    A bovine herpesvirus 1 (BHV-1) isolate from the semen of a subclinically infected bull was administered to cattle by various routes to assess its virulence. Cattle that were artificially inseminated or inoculated intrapreputially did not develop clinical signs, but did transmit the virus to contact

  20. High frequency intergenomic recombination of suid herpesvirus 1 (SHV-1, Aujeszkys-disease virus)

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Lomniczi, B.

    1993-01-01

    Examples are given of observations made with field isolates of suid herpesvirus 1 (SHV-1) which indicate that intergenomic recombination is a common phenomenon associated with the virus. This was further confirmed by experimental co-infection of a pig with 2 virus strains with different, stable...

  1. The genomic diversity and stability of field strains of Suid herpesvirus 1 (Aujeszky's disease virus)

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Sørensen, K. J.

    1991-01-01

    The genomic diversity among isolates of suid herpesvirus 1 (SHV-1) collected in the same herd and among clones from the same isolate was studied by restriction fragment pattern (RFP) analysis using BamHI. Tentatively defining a field strain as a transmissible entity, it was concluded that strains...

  2. Emydid herpesvirus 1 infection in northern map turtles (Graptemys geographica) and painted turtles (Chrysemys picta).

    Science.gov (United States)

    Ossiboff, Robert J; Newton, Alisa L; Seimon, Tracie A; Moore, Robert P; McAloose, Denise

    2015-05-01

    A captive, juvenile, female northern map turtle (Graptemys geographica) was found dead following a brief period of weakness and nasal discharge. Postmortem examination identified pneumonia with necrosis and numerous epithelial, intranuclear viral inclusion bodies, consistent with herpesviral pneumonia. Similar intranuclear inclusions were also associated with foci of hepatocellular and splenic necrosis. Polymerase chain reaction (PCR) screening of fresh, frozen liver for the herpesviral DNA-dependent DNA polymerase gene yielded an amplicon with 99.2% similarity to recently described emydid herpesvirus 1 (EmyHV-1). Molecular screening of turtles housed in enclosures that shared a common circulation system with the affected map turtle identified 4 asymptomatic, EmyHV-1 PCR-positive painted turtles (Chrysemys picta) and 1 asymptomatic northern map turtle. Herpesvirus transmission between painted and map turtles has been previously suggested, and our report provides the molecular characterization of a herpesvirus in asymptomatic painted turtles that can cause fatal herpesvirus-associated disease in northern map turtles. © 2015 The Author(s).

  3. Further evidence of Chelonid herpesvirus 5 (ChHV5) latency

    DEFF Research Database (Denmark)

    Alfaro Nuñez, Luis Alonso; Bojesen, Anders Miki; Bertelsen, Mads Frost

    2016-01-01

    The Chelonid herpesvirus 5 (ChHV5) has been consistently associated with fibropapillomatosis (FP), a transmissible neoplastic disease of marine turtles. Whether ChHV5 plays a causal role remains debated, partly because while FP tumours have been clearly documented to contain high concentrations...

  4. The coinfection between herpesviruses and periodontopathic microbiota in increasing severity of chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Mohammad Mukhit Abdul Gaffar Kazi

    2018-01-01

    Conclusion: Coinfection helps in the increasing severity of chronic periodontitis when a particular combination of herpesviruses and periodontopathic microbiota is detected from the cases of chronic periodontitis. Herpes simplex virus-2 and P. gingivalis seem to play a crucial role in the increasing severity of chronic periodontitis as compared to other coinfection combinations in the studied populations.

  5. Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

    NARCIS (Netherlands)

    Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

    2002-01-01

    In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control

  6. The isolation and partial characterization of a highly pathogenic herpesvirus from the harbor seal (Phoca vitulina).

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); H. Yang (Hong); H.E.M. Spijkers (Ine); J. Groen (Jan); J.S. Teppema; G. van Steenis (Bert)

    1985-01-01

    textabstractThis report describes the first isolation and partial characterization of a herpesvirus from the harbor seal (Phoca vitulina). The virus was isolated during a disease outbreak in a group of young seals nursed in a seal orphanage in The Netherlands. Almost half of the seals died with

  7. Equine herpesvirus 1 and/or 4 in working equids: se- roprevalence ...

    African Journals Online (AJOL)

    EHV-1 and EHV-4 were found to be prevalent in working equids in central. Ethiopia ..... and Equine Herpesvirus-1/-4 in the Spanish Purebred horse population in central. Spain: Risk factors and association with reproductive problems. PHD Thesis. Fac- ultad De Veterinaria. Universidad Complutense De Madrid, Madrid.

  8. Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma.

    Science.gov (United States)

    Di Bartolo, Daniel L; Hyjek, Elizabeth; Keller, Shannon; Guasparri, Ilaria; Deng, Hongyu; Sun, Ren; Chadburn, Amy; Knowles, Daniel M; Cesarman, Ethel

    2009-05-01

    Primary effusion lymphoma (PEL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Despite having a genotype and gene expression signature of highly differentiated B cells, PEL does not usually express surface or cytoplasmic immunoglobulin (Ig). We show the lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this defect in Ig production. Like Ig genes, ORF50, the key regulator of the switch from latency to lytic reactivation, contains an octamer motif within its promoter. We therefore examined the impact of Oct-2 and OCA-B on ORF50 activation. The binding of Oct-1 to the ORF50 promoter has been shown to significantly enhance ORF50 transactivation. We found that Oct-2, on the other hand, inhibited ORF50 expression and consequently lytic reactivation by competing with Oct-1 for the octamer motif in the ORF50 promoter. Our data suggest that Oct-2 downregulation in infected cells would be favorable to KSHV in allowing for efficient viral reactivation.

  9. Genetic characterization of complete open reading frame of glycoprotein C gene of bovine herpesvirus 1

    Directory of Open Access Journals (Sweden)

    Saurabh Majumder

    2013-10-01

    Full Text Available Aim: To characterize one of the major glycoprotein genes viz., glycoprotein C (gC; UL44, unique long region 44 of bovineherpesvirus 1(BoHV1 of Indian origin at genetic and phylogenetic level.Materials and Methods: A bovine herpesvirus 1 isolate viz., (BoHV1/IBR 216 II/ 1976/ India maintained at Division ofVirology, IVRI, Mukteswar was used for the current study. The DNA was extracted using commercial kit and the completeORF of gC gene was amplified, cloned, and sequenced by conventional Sanger sequencing method. The sequence wasgenetically and phylogenetically analysed using various bioinformatic tools. The sequence was submitted in the Genbankwith accession number Kc756965.Results: The complete ORF of gC gene was amplified and sequenced. It showed 100% sequence homology with referencecooper strain of BoHV1 and divergence varied from 0% to 2.7% with other isolates of BoHV1. The isolate under study haddivergence of 9.2%, 13%, 26.6%, and 9.2% with BoHV5 (Bovine herpesvirus 5, CvHV1 (Cervid herpesvirus 1, CpHV1(Caprine herpesvirus 1, and BuHV1 (Bubaline herpesvirus 1, respectively.Conclusion: This is the first genetic characterization of complete open reading frame (ORF of glycoprotein C gene (UL44 ofIndian isolate of BoHV1. The gC gene of BoHV1 is highly conserved among all BoHV1 isolates and it can be used as a targetfor designing diagnostic primers for the specific detection of BoHV1.

  10. The genome of Chelonid herpesvirus 5 harbors atypical genes

    Science.gov (United States)

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within thealphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis

  11. CYTOKINES AND HERPESVIRUSES IN CHILDREN WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    G. F. Zheleznikova

    2015-01-01

    Full Text Available It was determined earlier (G.P. Ivanova, 2012 that a chronic course of leukoencephalitis in teenagers caused by inadequate response of cytokine system to the combination of two herpesviruses (HV — EBV and HHV-6, leads to the development of multiple sclerosis (MS in 44% of cases. The research objective was to characterize the cytokine response in children with MS with simultaneous screening of the presence of active HV infections. 39 children with the diagnosis “MS” were under observation, 34 of them had relapsing-remitting (RR MS, and 5 children had a progressing course of MS (PMS. Concentration of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ, and IL-4 was identified in blood serum and cerebrospinal liquid (CSF by enzyme-linked immunosorbent assay, HV DNA was revealed by PCR. Cytokine status in children with MS had some differences depending on the phase of the disease, clinical severity of the relapse and the course of MS. The relapse phase of RRMS was associated with the accumulation of IL-8, IL-10, and IL-6 in the blood, and index IFNγ/IL-4 modulations in accordance with the clinical severity of the relapse. A severe aggravation of the disease in children with PMS was accompanied by the increase of IL-8 system response. HV DNA was revealed in 27 patients from 39 ones (69% in blood and in 17 patients (44% in CSF with the predominance of EBV (93%, frequently in combination with HHV-6. During an acute period the frequency of HV DNA identification increased 2–3 times to compare with the remission period. Unlike children with RRMS, a mixed-infection of 3–4 herpes viruses was revealed in all 5 patients with PMS. According to the results summary it is possible to make a conclusion that HV-infection has an important role in MS pathogenesis in teenagers, taking part in the aggravation and progression of the disease by its effect on the cytokine system response. EBV-infection dominates among HV, however the risk of MS development

  12. Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes

    International Nuclear Information System (INIS)

    Kelley-Clarke, Brenna; Ballestas, Mary E.; Komatsu, Takashi; Kaye, Kenneth M.

    2007-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes

  13. Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

    International Nuclear Information System (INIS)

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki; Oritani, Kenji; Matsuda, Tadashi

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR

  14. Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

    Energy Technology Data Exchange (ETDEWEB)

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan); Oritani, Kenji [Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Matsuda, Tadashi, E-mail: tmatsuda@pharm.hokudai.ac.jp [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan)

    2015-07-31

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

  15. Detection of Equid herpesvirus type 2 and 5 DNA in uterine flushings of mares with reproductive disorders.

    Science.gov (United States)

    Marenzoni, Maria Luisa; Sforna, Monica; Stefanetti, Valentina; Casagrande Proietti, Patrizia; Brignone, Luca; Del Sero, Andrea; Falcioni, Fabio; Orvieto, Simona; Tamantini, Cristina; Tiburzi, Alessandra; Valentini, Silvia; Coletti, Mauro; Timoney, Peter J; Passamonti, Fabrizio

    2014-12-05

    In recent years, there has been increasing evidence of the potential pathogenic significance of equine gammaherpesviruses in the horse. In humans, cattle and mice, gammaherpesviruses have already been associated with uterine infection. The aim of the present study was to investigate the presence of gammaherpesviruses in uterine flushings of mares with reproductive problems and to evaluate if there was a possible statistical association with clinical and laboratory findings in these cases. A total of 80 uterine flushings were collected from 61 mares with different reproductive problems and these were tested for equine herpesviruses (EHV) 1-5 by PCR. In the case of each mare in the study, the age, history of infertility, presence of anatomical defects in the reproductive tract, presence of systemic or local disease at time of sampling, phase in the oestrous cycle, post-partum interval, nature of uterine lavage performed (low versus large volume lavage), cytological and bacteriological examination results from the uterine flushing, and PCR herpesvirus results were recorded. Univariate analysis and multivariable logistic regression models were used to identify possible statistical associations and risk factors. Nine out of 61 mares (14.7%) had EHV-5 DNA in their uterine flushings. Co-infections with EHV-1 and EHV-2 were present in two cases. Of all the variables analyzed, only the cytological examination findings were associated with EHV-5 PCR positive results, both on univariate and multivariable analysis, especially in cases with an inflammation score of 3. It is postulated that presence of EHV-5 infection in the non-pregnant uterus may have a role to play in reproductive dysfunction and have a negative consequence on the pregnant uterus. Additional studies involving both healthy mares and mares with reproductive problems need to be performed, however, to elucidate whatever role equine gammaherpesviruses may play in the reproductive tract. This would be very

  16. Investigation of latent infections caused by cyprinid herpesvirus 3 in koi ( Cyprinus carpio) in southern China.

    Science.gov (United States)

    Zheng, Shucheng; Wang, Qing; Bergmann, Sven M; Li, Yingying; Zeng, Weiwei; Wang, Yingying; Liu, Chun; Shi, Cunbin

    2017-05-01

    Although herpesviruses such as cyprinid herpesvirus 3 (CyHV-3) can establish lifelong latent infections, little is known about latency conditions in farmed koi populations in China. We used nested polymerase chain reaction targeting the TK gene and an indirect antibody ELISA to screen asymptomatic fish obtained from southern China for evidence of CyHV-3 infection. CyHV-3 DNA could be detected either in peripheral blood leukocytes or from gills of asymptomatic koi. Most koi sera did not contain anti-CyHV-3 antibodies; however, 5 samples were ELISA positive, providing evidence of prior CyHV-3 infections. These findings suggest that koi may survive CyHV-3 infections and become virus carriers.

  17. Psittacid herpesvirus 3 infection in the eclectus parrot (Eclectus roratus) in Australia.

    Science.gov (United States)

    Gabor, M; Gabor, L J; Peacock, L; Srivastava, M; Rosenwax, A; Phalen, D

    2013-11-01

    Psittacid herpesvirus 3 (PsHV-3) has recently been implicated as the cause of a severe respiratory disease in Bourke's parrots (Neopsephotus bourkii) in the United States. In this report, the clinical manifestations and gross and microscopic lesions of PsHV-3 infection in 2 eclectus parrots (Eclectus roratus) in Australia are described. The presence of a PsHV-3 infection was confirmed by polymerase chain reaction amplification and sequencing of PsHV-3 DNA using degenerate and PsHV-3 primers. Electron microscopy of infected cells demonstrated the assembly of herpesvirus virions as well as intranuclear tubular structures. The detection of PsHV-3 in Australia in 2 eclectus parrots broadens the list of known affected species and confirms the presence of this virus in Australia.

  18. The prevalence of ovine herpesvirus-2 in 4 sheep breeds from different regions in South Africa

    Directory of Open Access Journals (Sweden)

    C.W. Bremer

    2010-05-01

    Full Text Available About 90% of bovine malignant catarrhal fever (BMCF PCR-positive cases in South Africa are caused by alcelaphine herpesvirus-1 (AlHV-1 and the other 10 % by ovine herpesvirus-2 (OvHV-2. The prevalence of OvHV-2 in different sheep breeds in South Africa was determined in order to investigate whether the lower incidence of BMCF caused by OvHV-2 in comparison with AlHV-1 can be ascribed to a low incidence of the virus in sheep. A single-tube hemi-nested PCR was developed, evaluated and applied to detect OvHV-2 DNA. The prevalence of the virus in 4 sheep breeds from various regions in South Africa was shown to be 77 %. No statistically significant difference was found amongst the sheep breeds tested.

  19. Genetic and biochemical characterization of the thymidine kinase gene from herpesvirus of turkeys

    International Nuclear Information System (INIS)

    Martin, S.L.; Aparisio, D.I.; Bandyopadhyay, P.K.

    1989-01-01

    The thymidine kinase gene encoded by herpesvirus of turkeys has been identified and characterized. A viral mutant (ATR 0 ) resistant to 1-β-D-arabinofuranosylthymine was isolated. This mutant was also resistant to 1-(2-fluoro-2-deoxy-β-D-arabinofuronosyl)-5-methyluracil and was unable to incorporate [ 125 I]deoxycytidine into DNA. The mutant phenotype was rescued by a cloned region of the turkey herpesvirus genome whose DNA sequence was found to contain an open reading frame similar to that for known thymidine kinases from other viruses. When expressed in Escherichia coli, this open reading frame complemented a thymidine kinase-deficient strain and resulted in thymidine kinase activity in extracts assayed in vitro

  20. Complete genome sequence and architecture of crucian carp Carassius auratus herpesvirus (CaHV).

    Science.gov (United States)

    Zeng, Xiao-Tao; Chen, Zhong-Yuan; Deng, Yuan-Sheng; Gui, Jian-Fang; Zhang, Qi-Ya

    2016-12-01

    Crucian carp Carassius auratus herpesvirus (CaHV) was isolated from diseased crucian carp with acute gill hemorrhages and high mortality. The CaHV genome was sequenced and analyzed. The data showed that it consists of 275,348 bp and contains 150 predicted ORFs. The architecture of the CaHV genome differs from those of four cyprinid herpesviruses (CyHV1, CyHV2, SY-C1, CyHV3), with insertions, deletions and the absence of a terminal direct repeat. Phylogenetic analysis of the DNA polymerase sequences of 17 strains of Herpesvirales members, and the concatenated 12 core ORFs from 10 strains of alloherpesviruses showed that CaHV clustered together with members of the genus Cyprinivirus, family Alloherpesviridae.

  1. Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication

    OpenAIRE

    Balistreri, Giuseppe; Viiliainen, Johanna; Turunen, Mikko; Diaz, Raquel; Lyly, Lauri; Pekkonen, Pirita; Rantala, Juha; Ojala, Krista; Sarek, Grzegorz; Teesalu, Mari; Denisova, Oxana; Peltonen, Karita; Julkunen, Ilkka; Varjosalo, Markku; Kainov, Denis

    2016-01-01

    Kaposi?s sarcoma herpesvirus (KSHV) causes Kaposi?s sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored...

  2. Differentially regulated splice variants and systems biology analysis of Kaposi's sarcoma-associated herpesvirus-infected lymphatic endothelial cells.

    Science.gov (United States)

    Chang, Ting-Yu; Wu, Yu-Hsuan; Cheng, Cheng-Chung; Wang, Hsei-Wei

    2011-09-01

    Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but little is known about the AS variations induced by KSHV. We analyzed KSHV-controlled AS using high-density microarrays capable of detecting all exons in the human genome. Splicing variants and altered exon-intron usage in infected LEC were found, and these correlated with protein domain modification. The different 3'-UTR used in new transcripts also help isoforms to escape microRNA-mediated surveillance. Exome-level analysis further revealed information that cannot be disclosed using classical gene-level profiling: a significant exon usage difference existed between LEC and CD34(+) precursor cells, and KSHV infection resulted in LEC-to-precursor, dedifferentiation-like exon level reprogramming. Our results demonstrate the application of exon arrays in systems biology research, and suggest the regulatory effects of AS in endothelial cells are far more complex than previously observed. This extra layer of molecular diversity helps to account for various aspects of endothelial biology, KSHV life cycle and disease pathogenesis that until now have been unexplored.

  3. microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.

    Directory of Open Access Journals (Sweden)

    Sunantha Sethuraman

    2017-07-01

    Full Text Available Kaposi's sarcoma (KS is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi's sarcoma-associated herpesvirus (KSHV is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL. In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs. The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.

  4. Detection of a nuclear, EBNA-type antigen in apparently EBNA-negative Herpesvirus papio (HVP)-transformed lymphoid lines by the acid-fixed nuclear binding technique.

    Science.gov (United States)

    Ohno, S; Luka, J; Falk, L; Klein, G

    1977-12-15

    In agreement with the findings of previous authors, we could not detect a virally determined nuclear antigen in Herpesvirus papio (HVP)-transformed baboon lymphoid lines by anticomplementary staining in situ, as for EBNA. However, by means of our recently developed acid-fixed nuclear binding technique an EBNA-like antigen could be readily demonstrated, after extraction from both producer and non-producer lines. We propose to designate the antigen as HUPNA. It can be detected by a human anti-EBNA antibody, suggesting cross-reactivity, if not identity, between EBNA and HUPNA. HVP-DNA carrying non-producer lines, negative for in situ ACIF stainability but capable of yielding HUPNA by the nuclear binding technique, can be superinfected with EBV, with brilliant EBNA expression as the result, suggesting that the defective in situ staining is a property associated with the baboon HVP, rather than the baboon lymphoid cell per se.

  5. Isolation and serological differentiation of a herpesvirus from bobwhite quail (Colinus virginianus, L. 1758).

    Science.gov (United States)

    Kaleta, E F; Marschall, H J; Glünder, G; Stiburek, B

    1980-01-01

    An infectious agent was isolated from the liver of bobwhite quails (Colinus virginianus, L. 1758). The agent was sensitive to chloroform and its multiplication was inhibited by 5-iodine-2-deoxy-uridine. It passed filters with a pore diameter of 220 nm and more but not 100 nm filters. Electron microscopic examination revealed numerous nucleocapsids with hollow capsomeres and few enveloped particles in the supernatant fluids of infected cultures. The nucleocapsids were calculated to have 162 capsomeres on their surface. Using the plaque reduction method for neutralization tests no serological cross reactions could be detected between the quail isolate and sera against Marek's disease virus, turkey herpes-virus (HV), duck enteritis HV, infectious laryngotracheitis HV, amazon parrot HV, great horned owl HV, eagle owl HV, snowy owl HV, falcon HV, pigeon HV, Lake Victoria Cormorant HV, and stork HV. The isolate from bobwhite quail did only cross-react with antiserum against crane HV. It is concluded that the isolated virus is a member of the avian herpesvirus group and it is proposed to tentatively term it herpesvirus colinum (from Colinus virginianus = bobwhite quail).

  6. Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

    Directory of Open Access Journals (Sweden)

    Fuqu Yu

    2007-03-01

    Full Text Available The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

  7. Herpesvirus-like respiratory infection in African penguins Spheniscus demersus admitted to a rehabilitation centre.

    Science.gov (United States)

    Parsons, Nola J; Gous, Tertius A; van Wilpe, Erna; Strauss, Venessa; Vanstreels, Ralph Eric

    2015-10-16

    Rehabilitation is an important strategy for the conservation of the Endangered African penguin Spheniscus demersus, and disease has been raised as a concern in the management of the species, both in the wild and in rehabilitation centres. We report 8 cases of herpesvirus-like respiratory infection in African penguin chicks undergoing rehabilitation between 2010 and 2013 at a facility in Cape Town, South Africa. Infection was confirmed through the identification of viral inclusions in the tracheal epithelium and demonstration of particles consistent with herpesvirus by electron microscopy, whereas virus isolation in eggs, serology and PCR testing failed to detect the virus. Only penguin chicks were affected; they were in poor body condition, and in 2 cases infection occurred prior to admission to the rehabilitation centre. The role played by the herpesvirus-like infection in the overall respiratory disease syndrome is uncertain, due to identification of lesions in only a small proportion of the chicks as well as to the occurrence of other concurrent pathological processes. Further studies are advised to characterise the specific virus involved through the development of sensitive diagnostic methods and to clarify the epidemiology and significance of these infections in wild African penguins.

  8. Characteristics of cyprinid herpesvirus 3 in different phases of infection: implications for disease transmission and control.

    Science.gov (United States)

    Sunarto, Agus; McColl, Kenneth A; Crane, Mark St J; Schat, Karel A; Slobedman, Barry; Barnes, Andrew C; Walker, Peter J

    2014-08-08

    Koi herpesvirus disease (KHVD) is an emerging and highly contagious viral disease of koi and common carp (Cyprinus carpio), causing mass mortalities and huge economic losses to the carp aquaculture industry. The disease has spread rapidly to 28 countries worldwide. However, mechanisms of koi herpesvirus (species Cyprinid herpesvirus 3; CyHV-3) transmission remain unclear. A potential experimental model of CyHV-3 infection in carp was used to characterise CyHV-3 in different phases of infection and to demonstrate that CyHV-3 persists in survivor fish and has the capacity to reactivate and transmit the disease to healthy fish. During acute infection, which occurred when fish were maintained at 22°C, viral genes were abundantly expressed and infectious virus was produced in association with tissue damage, clinical disease and mortality. In fish maintained at a lower temperature (11°C), viral DNA was present but viral gene expression was absent or greatly restricted, infectious virus was not recovered and there was no evidence of disease. Productive replication was re-initiated following an increase in water temperature to 22°C, resulting in 45% mortality. Shedding of reactivated virus killed 75% of cohabitating naïve fish, suggesting a potential risk for disease transmission. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  9. Equid herpesvirus 9 (EHV-9) isolates from zebras in Ontario, Canada, 1989 to 2007.

    Science.gov (United States)

    Rebelo, Ana Rita; Carman, Susy; Shapiro, Jan; van Dreumel, Tony; Hazlett, Murray; Nagy, Éva

    2015-04-01

    The objective of this study was to identify and partially characterize 3 equid herpesviruses that were isolated postmortem from zebras in Ontario, Canada in 1989, 2002, and 2007. These 3 virus isolates were characterized by plaque morphology, restriction fragment length polymorphism (RFLP) of their genomic deoxyribonucleic acid (DNA), real-time polymerase chain reaction (PCR) assay, and sequence analyses of the full length of the glycoprotein G (gG) gene (ORF70) and a portion of the DNA polymerase gene (ORF30). The isolates were also compared to 3 reference strains of equid herpesvirus 1 (EHV-1). Using rabbit kidney cells, the plaques for the isolates from the zebras were found to be much larger in size than the EHV-1 reference strains. The RFLP patterns of the zebra viruses differed among each other and from those of the EHV-1 reference strains. Real-time PCR and sequence analysis of a portion of the DNA polymerase gene determined that the herpesvirus isolates from the zebras contained a G at nucleotide 2254 and a corresponding N at amino acid position 752, which suggested that they could be neuropathogenic EHV-1 strains. However, subsequent phylogenetic analysis of the gG gene suggested that they were EHV-9 and not EHV-1.

  10. Isolation and characterization of an atypical Siberian sturgeon herpesvirus strain in Russia: novel North American Acipenserid herpesvirus 2 strain in Europe?

    Science.gov (United States)

    Doszpoly, A; Kalabekov, I M; Breyta, R; Shchelkunov, I S

    2017-10-01

    Siberian sturgeon herpesvirus (SbSHV) was isolated in Russia for the first time in 2006. Nine SbSHV isolates were recovered from different fish hatcheries producing the same cytopathic effect in cell cultures, the same clinical signs and mortality kinetics in virus-infected fish and the same virus neutralization pattern and shared identical nucleotide sequences. In 2011, a new isolate was recovered from juvenile sturgeon, which caused completely different cytopathic effect. That isolate was not readily neutralized by Siberian sturgeon hyperimmune antisera, and its DNA was not recognized by the routine PCR developed for SbSHV detection. Molecular study of the novel isolate revealed that it was more closely related to North American Acipenserid herpesvirus 2 (AciHV-2) isolates from white sturgeon, while the genome sequences of the former SbSHV isolates showed high similarity to the AciHV-2 isolated from shortnose sturgeon. While clinical signs and mortality caused by the novel isolate in infected Siberian sturgeon were similar to those of the formerly described SbSHV isolates, the incubation period and mean time to death produced by the novel isolate were twice as long. The differences between the former isolates and the recent one suggest that a novel SbSHV strain emerged in Europe and the molecular findings imply its North American origin. © 2017 John Wiley & Sons Ltd.

  11. The Murid Herpesvirus-4 gL regulates an entry-associated conformation change in gH.

    Directory of Open Access Journals (Sweden)

    Laurent Gillet

    2008-07-01

    Full Text Available The glycoprotein H (gH/gL heterodimer is crucial for herpesvirus membrane fusion. Yet how it functions is not well understood. The Murid Herpesvirus-4 gH, like that of other herpesviruses, adopts its normal virion conformation by associating with gL. However, gH switched back to a gL-independent conformation after virion endocytosis. This switch coincided with a conformation switch in gB and with capsid release. Virions lacking gL constitutively expressed the down-stream form of gH, prematurely switched gB to its down-stream form, and showed premature capsid release with poor infectivity. These data argue that gL plays a key role in regulating a gH and gB functional switch from cell binding to membrane fusion.

  12. Pneumonia in calves produced with aerosols of Pasteurella multocida alone and in combination with bovine herpesvirus 1.

    OpenAIRE

    Jericho, K W; Carter, G R

    1985-01-01

    Pathological changes in respiratory tracts were studied in 30 calves following exposure to aerosols of Pasteurella multocida or to bovine herpesvirus 1 and P. multocida. Two groups of five calves were exposed to aerosols of one of two types of P. multocida only, which produced lobar pneumonia in one calf of each group. Another five groups of four calves were exposed to aerosols of bovine herpesvirus 1 and four to seven days later to one of the two types or one sub-type of P. multocida. Extens...

  13. Two Different Macaviruses, ovine herpesvirus-2 and caprine herpesvirus-2, behave differently in water buffaloes than in cattle or in their respective reservoir species.

    Directory of Open Access Journals (Sweden)

    Anina B J Stahel

    Full Text Available The ongoing global spread of "exotic" farm animals, such as water buffaloes, which carry their native sets of viruses, may bear unknown risks for the animals, into whose ecological niches the former are introduced and vice versa. Here, we report on the occurrence of malignant catarrhal fever (MCF on Swiss farms, where "exotic" water buffaloes were kept together with "native" animals, i.e. cattle, sheep, and goats. In the first farm with 56 water buffaloes, eight cases of MCF due to ovine herpesvirus-2 (OvHV-2 were noted, whereas additional ten water buffaloes were subclinically infected with either OvHV-2 or caprine herpesvirus-2 (CpHV-2. On the second farm, 13 water buffaloes were infected with CpHV-2 and two of those succumbed to MCF. In neither farm, any of the two viruses were detected in cattle, but the Macaviruses were present at high prevalence among their original host species, sheep and goats, respectively. On the third farm, sheep were kept well separated from water buffaloes and OvHV-2 was not transmitted to the buffaloes, despite of high prevalence of the virus among the sheep. Macavirus DNA was frequently detected in the nasal secretions of virus-positive animals and in one instance OvHV-2 was transmitted vertically to an unborn water buffalo calf. Thus, water buffaloes seem to be more susceptible than cattle to infection with either Macavirus; however, MCF did not develop as frequently. Therefore, water buffaloes seem to represent an interesting intermediate-type host for Macaviruses. Consequently, water buffaloes in their native, tropic environments may be vulnerable and endangered to viruses that originate from seemingly healthy, imported sheep and goats.

  14. Clinical protection against caprine herpesvirus 1 genital infection by intranasal administration of a live attenuated glycoprotein E negative bovine herpesvirus 1 vaccine

    Directory of Open Access Journals (Sweden)

    Meurens François

    2007-12-01

    Full Text Available Abstract Background Caprine herpesvirus 1 (CpHV-1 is responsible of systemic diseases in kids and genital diseases leading to abortions in goats. CpHV-1 is widespread and especially in Mediterranean countries as Greece, Italy and Spain. CpHV-1 is antigenically and genetically closely related to bovine herpesvirus 1 (BoHV-1. Taking into account the biological properties shared by these two viruses, we decided in the current study to assess the protection of a live attenuated glycoprotein E (gE negative BoHV-1 vaccine against a genital CpHV-1 infection in goats. Results The vaccine was inoculated intranasally twice three weeks apart followed by a subsequent CpHV-1 intravaginal challenge which is the natural route of infection in three goats. To analyse the safety and the efficacy of this marker vaccine, two groups of three goats served as controls: one immunised with a virulent CpHV-1 and one uninoculated until the challenge. Goats were clinically monitored and all sampling procedures were carried out in a blind manner. The vaccine did not induce any undesirable local or systemic reaction and goats did not excrete gE-negative BoHV-1. After challenge, a significant reduction in disease severity was observed in immunised goats. Moreover, goats immunised with either gE-negative BoHV-1 or CpHV-1 exhibited a significant reduction in the length and the peak of viral excretion. Antibodies neutralising both BoHV-1 and CpHV-1 were raised in immunised goats. Conclusion Intranasal application of a live attenuated gE-negative BoHV-1 vaccine is able to afford a clinical protection and a reduction of virus excretion in goats challenged by a CpHV-1 genital infection.

  15. Equid herpesvirus 8: Complete genome sequence and association with abortion in mares

    Science.gov (United States)

    Garvey, Marie; Suárez, Nicolás M.; Kerr, Karen; Hector, Ralph; Moloney-Quinn, Laura; Arkins, Sean; Davison, Andrew J.

    2018-01-01

    Equid herpesvirus 8 (EHV-8), formerly known as asinine herpesvirus 3, is an alphaherpesvirus that is closely related to equid herpesviruses 1 and 9 (EHV-1 and EHV-9). The pathogenesis of EHV-8 is relatively little studied and to date has only been associated with respiratory disease in donkeys in Australia and horses in China. A single EHV-8 genome sequence has been generated for strain Wh in China, but is apparently incomplete and contains frameshifts in two genes. In this study, the complete genome sequences of four EHV-8 strains isolated in Ireland between 2003 and 2015 were determined by Illumina sequencing. Two of these strains were isolated from cases of abortion in horses, and were misdiagnosed initially as EHV-1, and two were isolated from donkeys, one with neurological disease. The four genome sequences are very similar to each other, exhibiting greater than 98.4% nucleotide identity, and their phylogenetic clustering together demonstrated that genomic diversity is not dependent on the host. Comparative genomic analysis revealed 24 of the 76 predicted protein sequences are completely conserved among the Irish EHV-8 strains. Evolutionary comparisons indicate that EHV-8 is phylogenetically closer to EHV-9 than it is to EHV-1. In summary, the first complete genome sequences of EHV-8 isolates from two host species over a twelve year period are reported. The current study suggests that EHV-8 can cause abortion in horses. The potential threat of EHV-8 to the horse industry and the possibility that donkeys may act as reservoirs of infection warrant further investigation. PMID:29414990

  16. Kaposi's Sarcoma-Associated Herpesvirus | Center for Cancer Research

    Science.gov (United States)

    The discovery of KSHV in 1994 was a historical landmark in tumor virology and human cancer research. KSHV's subsequent identification as a cause of Kaposi sarcoma and its association with primary effusion lymphoma and multicentric Castleman disease soon attracted the attention of hundreds of research laboratories and motivated thousands of virologists and oncologists to switch

  17. Generation and characterization of koi herpesvirus recombinants lacking viral enzymes of nucleotide metabolism.

    Science.gov (United States)

    Fuchs, Walter; Fichtner, Dieter; Bergmann, Sven M; Mettenleiter, Thomas C

    2011-06-01

    Koi herpesvirus (KHV) causes a fatal disease in koi and common carp, but no reliable and genetically characterized vaccines are available up to now. Therefore, we generated KHV recombinants possessing deletions within the viral ribonucleotide reductase (RNR), thymidine kinase (TK), dUTPase, or TK and dUTPase genes, and their corresponding rescuants. All KHV mutants were replication competent in cultured cells. Whereas plaque sizes and titers of RNR-negative KHV were reduced, replication of the other mutants was not affected. Experimental infection of carp indicated attenuation of TK- or dUTPase-deleted KHV, and PCR analysis of tissue samples permitted differentiation of mutant from wild-type virus.

  18. Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.

    Science.gov (United States)

    Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C

    2017-10-01

    Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here

  19. Inhibition of herpesvirus and influenza virus replication by blocking polymerase subunit interactions.

    Science.gov (United States)

    Palù, Giorgio; Loregian, Arianna

    2013-09-01

    Protein-protein interactions (PPIs) play a key role in many biological processes, including virus replication in the host cell. Since most of the PPIs are functionally essential, a possible strategy to inhibit virus replication is based on the disruption of viral protein complexes by peptides or small molecules that interfere with subunit interactions. In particular, an attractive target for antiviral drugs is the binding between the subunits of essential viral enzymes. This review describes the development of new antiviral compounds that inhibit herpesvirus and influenza virus replication by blocking interactions between subunit proteins of their polymerase complexes. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

    2011-01-01

    This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

  1. Identification of B cells as a major site for cyprinid herpesvirus 3 latency.

    Science.gov (United States)

    Reed, Aimee N; Izume, Satoko; Dolan, Brian P; LaPatra, Scott; Kent, Michael; Dong, Jing; Jin, Ling

    2014-08-01

    Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), is a member of the Alloherpesviridae, and is a recently discovered emerging herpesvirus that is highly pathogenic for koi and common carp. Our previous study demonstrated that CyHV-3 becomes latent in peripheral white blood cells (WBC). In this study, CyHV-3 latency was further investigated in IgM(+) WBC. The presence of the CyHV-3 genome in IgM(+) WBC was about 20-fold greater than in IgM(-) WBC. To determine whether CyHV-3 expressed genes during latency, transcription from all eight open reading frames (ORFs) in the terminal repeat was investigated in IgM(+) WBC from koi with latent CyHV-3 infection. Only a spliced ORF6 transcript was found to be abundantly expressed in IgM(+) WBC from CyHV-3 latently infected koi. The spliced ORF6 transcript was also detected in vitro during productive infection as early as 1 day postinfection. The ORF6 transcript from in vitro infection begins at -127 bp upstream of the ATG codon and ends +188 bp downstream of the stop codon, +20 bp downstream of the polyadenylation signal. The hypothetical protein of ORF6 contains a consensus sequence with homology to a conserved domain of EBNA-3B and ICP4 from Epstein-Barr virus and herpes simplex virus 1, respectively, both members of the Herpesviridae. This is the first report of latent CyHV-3 in B cells and identification of gene transcription during latency for a member of the Alloherpesviridae. This is the first demonstration that a member of the Alloherpesviridae, cyprinid herpesvirus 3 (CyHV-3), establishes a latent infection in the B cells of its host, Cyprinus carpio. In addition, this is the first report of identification of gene transcription during latency for a member of Herpesvirales outside Herpesviridae. This is also the first report that the hypothetical protein of latent transcript of CyHV-3 contains a consensus sequence with homology to a conserved domain of EBNA-3B from Epstein-Barr virus and ICP4

  2. Subclinical infection of a young captive Asian elephant with elephant endotheliotropic herpesvirus 1.

    Science.gov (United States)

    Azab, Walid; Damiani, Armando Mario; Ochs, Andreas; Osterrieder, Nikolaus

    2018-02-01

    Elephant endotheliotropic herpesviruses (EEHVs) are a continuous threat for young Asian elephants. We report a laboratory-confirmed infection of a 5-year-old female Asian elephant (AZ_2016) in the Berlin Zoologischer Garten. Initially, high EEHV-1 loads were detected in trunk swabs obtained from the young elephant during routine screening. The animal showed no clinical signs except for slight irritability. EEHV-1 was continuously shed for almost one year, with fluctuations in viral load from time to time. Our investigations highlight the continuous threat of EEHV-1 to young captive Asian elephants and stress the importance of routine monitoring of captive elephants to allow early detection of infection.

  3. Elephant Endotheliotropic Herpesviruses EEHV1A, EEHV1B, and EEHV2 from Cases of Hemorrhagic Disease Are Highly Diverged from Other Mammalian Herpesviruses and May Form a New Subfamily

    Science.gov (United States)

    Richman, Laura K.; Zong, Jian-Chao; Latimer, Erin M.; Lock, Justin; Fleischer, Robert C.; Heaggans, Sarah Y.

    2014-01-01

    ABSTRACT A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus Proboscivirus have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new Deltaherpesvirinae subfamily of mammalian herpesviruses that evolved as an intermediate branch between the Betaherpesvirinae and Gammaherpesvirinae. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A. IMPORTANCE Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a

  4. Biological characterization of bovine herpesvirus 1 recombinants possessing the vaccine glycoprotein E negative phenotype.

    Science.gov (United States)

    Muylkens, Benoît; Meurens, François; Schynts, Frédéric; de Fays, Katalin; Pourchet, Aldo; Thiry, Julien; Vanderplasschen, Alain; Antoine, Nadine; Thiry, Etienne

    2006-03-31

    Intramolecular recombination is a frequent event during the replication cycle of bovine herpesvirus 1 (BoHV-1). Recombinant viruses frequently arise and survive in cattle after concomitant nasal infections with two BoHV-1 mutants. The consequences of this process, related to herpesvirus evolution, have to be assessed in the context of large use of live marker vaccines based on glycoprotein E (gE) gene deletion. In natural conditions, double nasal infections by vaccine and wild-type strains are likely to occur. This situation might generate virulent recombinant viruses inducing a serological response indistinguishable from the vaccine one. This question was addressed by generating in vitro BoHV-1 recombinants deleted in the gE gene from seven wild-type BoHV-1 strains and one mutant strain deleted in the genes encoding gC and gE. In vitro growth properties were assessed by virus production, one step growth kinetics and plaque size assay. Heterogeneity in the biological properties was shown among the investigated recombinant viruses. The results demonstrated that some recombinants, in spite of their gE minus phenotype, have biological characteristics close to wild-type BoHV-1.

  5. Utility of a Multiplex PCR Assay for Detecting Herpesvirus DNA in Clinical Samples

    Science.gov (United States)

    Druce, Julian; Catton, Mike; Chibo, Doris; Minerds, Kirsty; Tyssen, David; Kostecki, Renata; Maskill, Bill; Leong-Shaw, Wendy; Gerrard, Marie; Birch, Chris

    2002-01-01

    A multiplex PCR was designed to amplify herpes simplex virus types 1 and 2, cytomegalovirus, and varicella-zoster virus DNA present in a diverse range of clinical material. The susceptibility of these viruses to in vivo inhibition by at least one antiviral drug was an important consideration in their inclusion in the multiplex detection system. An aliquot of equine herpesvirus was introduced into each specimen prior to extraction and served as an indicator of potential inhibitors of the PCR and a detector of suboptimal PCR conditions. Compared to virus isolation and immunofluorescence-based antigen detection, the multiplex assay yielded higher detection rates for all viruses represented in the assay. The turnaround time for performance of the assay was markedly reduced compared to those for the other techniques used to identify these viruses. More than 21,000 tests have been performed using the assay. Overall, the multiplex PCR enabled the detection of substantially increased numbers of herpesviruses, in some cases in specimens or anatomical sites where previously they were rarely if ever identified using traditional detection methods. PMID:11980951

  6. Crystal structure of the conserved herpesvirus fusion regulator complex gH—gL

    Energy Technology Data Exchange (ETDEWEB)

    Chowdary, Tirumala K.; Cairns, Tina M.; Atanasiu, Doina; Cohen, Gary H.; Eisenberg, Roselyn J.; Heldwein, Ekaterina E. [UPENN; (Tufts-MED)

    2015-02-09

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH–gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH–gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH–gL activates gB for fusion, possibly through direct binding. Formation of a gB–gH–gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB–gH–gL interface a promising antiviral target.

  7. Concomitant infection of Neospora caninum and Bovine Herpesvirus type 5 in spontaneous bovine abortions

    Directory of Open Access Journals (Sweden)

    Maia S. Marin

    2013-11-01

    Full Text Available Bovine Herpesvirus type 5 (BoHV-5 has not been conclusively demonstrated to cause bovine abortion. Brain lesions produced by Neospora caninum and Bovine Herpesvirus type 1 (BoHV-1 exhibit common features. Therefore, careful microscopic evaluation and additional diagnostic procedures are required to achieve an accurate final etiological diagnosis. The aim of the present work was to investigate the occurrence of infections due to BoHV-1, BoHV-5 and N. caninum in 68 cases of spontaneous bovine abortions which showed microscopic lesions in the fetal central nervous system. This study allowed the identification of 4 (5.9% fetuses with dual infection by BoHV-5 and N. caninum and 33 (48.5% cases in which N. caninum was the sole pathogen identified. All cases were negative to BoHV-1. The results of this study provide evidence that dual infection by BoHV-5 and N. caninum occur during pregnancy in cattle; however, the role of BoHV-5 as a primary cause of bovine abortion needs further research. Molecular diagnosis of BoHV-5 and N. caninum confirmed the importance of applying complementary assays to improve the sensitivity of diagnosing bovine abortion.

  8. Prevention of equine herpesvirus myeloencephalopathy - Is heparin a novel option? A case report.

    Science.gov (United States)

    Walter, Jasmin; Seeh, Christoph; Fey, Kerstin; Bleul, Ulrich; Osterrieder, Nikolaus

    2016-10-12

    Equine herpesvirus myeloencephalopathy (EHM) is a severe manifestation of equine herpesvirus 1 (EHV-1) infection. Prevention and treatment of EHM during EHV-1 outbreaks is critical, but no reliable and tested specific medication is available. Due to the thromboischemic nature of EHM and due to the fact that EHV-1 entry in cells is blocked by heparin, it was hypothesized that this compound may be useful in reduction of EHM incidence and severity. Therefore, during an acute EHV-1 outbreak with the neuropathogenic G 2254 /D 752 Pol variant, metaphylactic treatment with heparin to prevent EHM was initiated. Clinical signs were present in 61 horses (fever n = 55; EHM n = 8; abortion n = 6). Heparin (25000 IU subcutaneously twice daily for 3 days) was given to 31 febrile horses from day 10 of the outbreak, while the first 30 horses exhibiting fever remained untreated. Treatment outcome was analyzed retrospectively. Heparin-treated horses showed a lower EHM incidence (1/31; 3.2%) than untreated horses (7/30; 23.3%; p = 0.03). Results indicate that heparin may be useful for prevention of EHM during an EHV-1 outbreak. These promising data highlight the need for randomized and possibly blinded studies for the use of heparin in EHV-1 outbreaks.

  9. Characterization of canine herpesvirus glycoprotein C expressed by a recombinant baculovirus in insect cells.

    Science.gov (United States)

    Xuan, X; Maeda, K; Mikami, T; Otsuka, H

    1996-12-01

    The gene encoding the canine herpesvirus (CHV) glycoprotein C (gC) homologue has been identified by sequence homology analyses with other well studied herpesviruses. Previously, we have identified three CHV glycoproteins, gp145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which CHV glycoprotein corresponds to gC, a recombinant baculovirus which contains the putative CHV gC structural gene under the baculovirus polyhedrin promoter was constructed. The recombinant baculovirus expressed gC-related polypeptides (44-62 kDa), which reacted only with MAbs against CHV gp80, indicating that the previously identified CHV gp80 is the translation product of the gC gene. The baculovirus expressed gC was glycosylated and transported to the surface of infected cells. At least seven neutralizing epitopes were conserved on the gC produced in insect cells. It was found that the recombinant baculovirus infected cells adsorbed murine erythrocytes as is the case for CHV-infected cells. The hemadsorption activity was inhibited by heparin, indicating that the CHV gC binds to heparan sulfate on the surface of murine erythrocytes. Mice immunized with the recombinant gC produced strong neutralizing antibodies. Our results suggest that CHV gC produced in insect cells may be useful as a subunit vaccine to control CHV infections.

  10. Ulcerative dermatitis caused by feline herpesvirus type 1 in a domestic cat

    Directory of Open Access Journals (Sweden)

    Fernando Froner Argenta

    2017-08-01

    Full Text Available A case of ulcerative dermatitis caused by feline herpesvirus type 1 (FeHV-1 in an adult male domestic shorthair cat is reported. The cat was rescued from the streets and presented with ulcerative lesions at the nasal planum and tongue in addition to a history of occasional sneezing. Thirty days after of the first clinical evaluation, the cat died as a result of acute myeloid leukemia. During necropsy, ulcerative lesions were found on the superior lip, the skin of the nasal planum, and at the periorbital region. Ulcerations were also noted on the tongue and hard palate. Histological examination revealed extensive epidermal necrosis, which involved the subjacent dermis and adnexal structures; the inflammatory infiltrate consisted of neutrophils, mast cells, and lymphocytes. Amphophilic intranuclear inclusion bodies were occasionally observed in intact epithelial cells. In the immunohistochemical evaluation, positive intracytoplasmic immunolabeling was detected in the sebaceous and follicular epithelial cells as well as in the bronchiolar epithelial cells. Samples of lymphoid tissue tested positive for the presence of feline leukemia virus and feline immunodeficiency virus by immunohistochemistry. Pulmonary tissue fragments were immunolabeled for feline calicivirus. Samples obtained from a cutaneous lesion were subjected to virus isolation in a cellular culture, which revealed the cytopathic effects characteristic of herpesvirus. FeHV-1 was detected in the samples by polymerase chain reaction.

  11. Isolation of caprine herpesvirus 1 from a major outbreak of infectious pustular vulvovaginitis in goats.

    Science.gov (United States)

    Piper, K L; Fitzgerald, C J; Ficorilli, N; Studdert, M J

    2008-04-01

    We describe an outbreak of infectious pustular vulvovaginitis caused by Caprine herpesvirus 1 (CpHV1) in a group of approximately 200, 8 month old virgin does that were imported to Victoria from New Zealand. CpHV1 was isolated in cell cultures from vaginal swabs from three of three affected does but not from two bucks that had been with the does. The identity of the virus as a herpesvirus was confirmed by negative stain electron microscopy. Restriction endonuclease DNA fingerprint analysis showed that the DNA fingerprints were similar, but not identical, to previously described CpHV1 isolates made in New Zealand, New South Wales, and in other parts of the world. Acute and convalescent phase sera from selected does supported the diagnosis of CpHV1 infection. It is most likely that the disease was initiated by reactivation of latent virus in at least one of four bucks that served the does, since each was positive for CpHV neutralising antibody when first tested. This is the first report of CpHV infectious pustular vulvovaginitis in goats in Victoria and to our knowledge appears to be one of the largest outbreaks recorded anywhere.

  12. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

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    Tzviya Zeev-Ben-Mordehai

    2015-12-01

    Full Text Available Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC, which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.

  13. Development of a PCR assay to detect cyprinid herpesvirus 1 in koi and common carp.

    Science.gov (United States)

    Viadanna, Pedro H O; Miller-Morgan, Tim; Peterson, Trace; Way, Keith; Stone, David M; Marty, Gary D; Pilarski, Fabiana; Hedrick, Ronald P; Waltzek, Thomas B

    2017-02-08

    Cyprinid herpesvirus 1 (CyHV1) infects all scaled and color varieties of common carp Cyprinus carpio, including koi. While it is most often associated with unsightly growths known as 'carp pox,' the underlying lesion (epidermal hyperplasia) can arise from a variety of disease processes. CyHV1-induced epidermal hyperplasia may occur transiently in response to water temperature, and thus histopathology cannot be used in isolation to assess CyHV1 infection status. To address this problem, here we describe a PCR assay targeted to the putative thymidine kinase gene of CyHV1. The PCR assay generates a 141 bp amplicon and reliably detects down to 10 copies of control plasmid DNA sequence (analytic sensitivity). The PCR does not cross-detect genomic DNA from cyprinid herpesvirus 2 and 3 (analytic specificity). The CyHV1 PCR effectively detected viral DNA in koi and common carp sampled from various locations in the UK, USA, Brazil, and Japan. Viral DNA was detected in both normal appearing and grossly affected epidermal tissues from koi experiencing natural epizootics. The new CyHV1 PCR provides an additional approach to histopathology for the rapid detection of CyHV1. Analysis of the thymidine kinase gene sequences determined for 7 PCR-positive carp originating from disparate geographical regions identified 3 sequence types, with 1 type occurring in both koi and common carp.

  14. Molecular characterisation and prevalence of a new genotype of Cyprinid herpesvirus 2 in mainland China.

    Science.gov (United States)

    Li, Lijuan; Luo, Yangzhi; Gao, Zexia; Huang, Jian; Zheng, Xianghai; Nie, Huihui; Zhang, Junmei; Lin, Li; Yuan, Junfa

    2015-06-01

    Cyprinid herpesvirus 2 (CyHV-2, species Cyprinid herpesvirus 2) has been confirmed as a causative agent of the acute haematopoietic necrosis disease outbreak in farmed goldfish (Carassius auratus L.) and gibel carp (Carassius auratus gibelio Bloch). In this study, we present the genomic characteristics of a variant CyHV-2 strain (SY-C1) isolated from farmed gibel carp in mainland China and its comparative genomics analysis with the CyHV-2 reference strain ST-J1. Overall, the full-length genome of SY-C1 shares 98.8% homology with that of ST-J1. Sequence comparisons between SY-C1 and ST-J1 indicate that the variations include single-nucleotide mutations, insertions, deletions, and rearrangements, which suggested that SY-C1 is different from ST-J1 and represents a new genotype. Therefore, we propose that the identified CyHV-2 can be divided into 2 different genotypes and be named China genotype (C genotype) and Japan genotype (J genotype) according to their isolation loci. Furthermore, epidemiological surveys indicate that the dominant genotype of CyHV-2 circulating in mainland China is closer to the China genotype than the Japan genotype.

  15. Potency of Garlic Extract Against Koi Herpesvirus (KHV in Common Carp

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    Sri Nuryati

    2007-07-01

    Full Text Available Prevention of koi herpesvirus (KHV infection using chemicals or medicines was ineffective way.  In this study garlic extract was used to prevent KHV infection.  Virus suspension of 0.1 ml and garlic extract of 0.1 ml in different dosage, i.e., 100, 200 and 300 ppt, was injected into common carp body.  Hemoglobin concentration, red and white blood cell numbers, and leukocyte number were counted.  The results of study showed that administration of 300 ppt of garlic extract could produce higher survival rate (67.5%, good blood parameters and clinical symptoms compared to other treatments. Keywords: garlic, KHV, common carp   ABSTRAK Upaya penanggulangan wabah Koi Herpesvirus (KHV menggunakan bahan-bahan kimia atau obat-obatan adalah tidak efektif. Pada penelitian ini dilakukan pemberian ekstrak bawang putih untuk menanggulangi infeksi KHV.  Suspensi virus sebanyak 0,1 ml ditambahkan dengan 0,1 ml ekstrak bawang putih dengan berbagai konsentrasi, yaitu 100, 200 dan 300 ppt, disuntikkan ke dalam tubuh ikan mas.  Kadar hemoglobin, jumlah sel darah merah dan sel darah putih jenis dan jumlah leukosit diamati. Hasil penelitian menunjukkan bahwa pemberian ekstrak bawang putih sebanyak 300 ppt menghasilkan kelangsungan hidup (67,5% yang lebih baik dibandingkan dengan perlakuan lainnya, dan begitu pula dengan gambaran darah serta gejala klinisnya.   Kata kunci: bawang putih, KHV, ikan mas

  16. Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication.

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    Giuseppe Balistreri

    2016-02-01

    Full Text Available Kaposi's sarcoma herpesvirus (KSHV causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.

  17. Cloning of Bovine herpesvirus type 1 and type 5 as infectious bacterial artifical chromosomes

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    Ackermann Mathias

    2009-10-01

    Full Text Available Abstract Background Bovine herpesviruses type 1 (BoHV1 and type 5 (BoHV5 are two closely related pathogens of cattle. The identity of the two viruses on the amino acid level averages 82%. Despite their high antigenetic similarities the two pathogens induce distinctive clinical signs. BoHV1 causes respiratory and genital tract infections while BoHV5 leads to severe encephalitis in calves. Findings The viral genomes of BoHV1 and BoHV5 were cloned as infectious bacterial artificial chromosomes (BACs. First, recombinant viruses carrying the genetic elements for propagation in bacteria were generated. Second, DNA from these recombinant viruses were transferred into prokaryotic cells. Third, DNA from these bacteria were transferred into eukaryotic cells. Progeny viruses from BAC transfections showed similar kinetics as their corresponding wild types. Conclusion The two viral genomes of BoHV1 and BoHV5 cloned as BACs are accessible to the tools of bacterial genetics. The ability to easily manipulate the viral genomes on a molecular level in future experiments will lead to a better understanding of the difference in pathogenesis induced by these two closely related bovine herpesviruses.

  18. Equine herpesvirus 2 (EHV-2 infection in thoroughbred horses in Argentina

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    Fernández Fernando M

    2005-11-01

    Full Text Available Abstract Background Equine herpesvirus 2 is a gamma-herpesvirus that infects horses worldwide. Although EHV-2 has been implicated in immunosuppression in foals, upper respiratory tract disease, conjunctivitis, general malaise and poor performance, its precise role as a pathogen remains uncertain. The purpose of the present study was to analyse the incidence of EHV-2 in an Argentinean horse population and correlate it with age and clinical status of the animals. Results A serological study on 153 thoroughbred racing horses confirmed the presence of EHV-2 in the Argentinean equine population. A virus neutralization test showed a total of 79.7 % animals were sero-positive for EHV-2. An increase in antibodies titre with age as well as infection at earlier ages were observed. EHV-2 was isolated from 2 out of 22 nasal swabs from horses showing respiratory symptoms. The virus grew slowly and showed characteristic cytopathic effect after several blind passages on RK13 cells. The identity of the isolates was confirmed by nested PCR and restriction enzyme assay (REA. Conclusion This is the first report on the presence of EHV-2 in Argentina and adds new data to the virus distribution map. Though EHV-2 was isolated from foals showing respiratory symptoms, further studies are needed to unequivocally associate this virus with clinical symptoms.

  19. Construction and characterization of a glycoprotein E deletion mutant of bovine herpesvirus type 1.2 strain isolated in Brazil

    NARCIS (Netherlands)

    Franco, A.C.; Rijsewijk, F.A.M.; Flores, E.F.; Weiblen, R.; Roehe, P.M.

    2002-01-01

    This paper describes the construction and characterization of a Brazilian strain of bovine herpesvirus type 1.2a (BoHV-1.2a) with a deletion of the glycoprotein E (gE) gene. The deletion was introduced by co-transfection of a deletion fragment containing the 5´and 3´gE flanking regions and genomic

  20. Experimental infection of calves with a gI, gE, US9 negative bovine herpesvirus type 5

    NARCIS (Netherlands)

    Hubner, S.O.; Oliveira, A.P.; Franco, A.C.; Rijsewijk, F.A.M.; Roehe, P.M.

    2005-01-01

    In this work, a role for the genes encoding glycoproteins I (gI) and E (gE) and the US9 protein of bovine herpesvirus type 5 (BHV-5) in neuropathogenicity and reactivation of latent infections was examined. Calves infected intranasally with a gI/gE/US9 deleted recombinant shed up to 102.85 TCID50/ml

  1. Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging

    Science.gov (United States)

    Cyprinid herpesvirus 3 (CyHV-3) is causing severe economic losses worldwide in the carp industry, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open...

  2. Detection of bovine herpesvirus 4 glycoprotein B and thymidine kinase DNA by PCR assays in bovine milk

    NARCIS (Netherlands)

    Wellenberg, G.J.; Verstraten, E.; Belak, S.; Verschuren, S.B.E.; Rijsewijk, F.A.M.; Peshev, R.; Oirschot, van J.T.

    2001-01-01

    A polymerase chain reaction (PCR) assay was developed to detect bovine herpesvirus 4 (BHV4) glycoprotein B (gB) DNA, and a nested-PCR assay was modified for the detection of BHV4 thymidine kinase (TK) DNA in bovine milk samples. To identify false-negative PCR results, internal control templates were

  3. Detection of Cyprinid herpesvirus 2 in association with an Aeromonas sobria infection of Carassius carassius (L.), in Italy

    DEFF Research Database (Denmark)

    Fichi, G.; Cardeti, G.; Cocumelli, C.

    2013-01-01

    herpesvirus‐like particles, subsequently identified as Cyprinid herpesvirus‐2 (CyHV‐2) with a nested PCR protocol. Although it was not possible to attribute a pathogenic role to CyHV‐2 in this mortality event, the identification of this herpesvirus in crucian carp increases the concern about its potential...

  4. Characterization of field isolates of Suid herpesvirus 1 (Aujeszky's disease virus) as derivatives of attenuated vaccine strains

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Medveczky, I.; Strandbygaard, Bertel

    1992-01-01

    Field isolates of suid herpesvirus 1 (Aujeszky's disease virus) from Poland and Hungary were identified by restriction fragment pattern analysis as derivatives of attenuated vaccine strains. The Polish isolates were found to be related to the BUK-TK-900 strain (Suivac A) which is widely used...

  5. Restriction Fragment Pattern (RFP) analysis of genomes from Danish isolates of Suid herpesvirus 1 (Aujeszky's disease virus)

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Sørensen, K. J.; Lei, J. C.

    1987-01-01

    Purified DNA from 42 isolates of Suid herpesvirus 1 (SHV-1) collected during 1985 from clinical outbreaks of Aujezsky's disease on Danish farms was compared by restriction fragment pattern (RFP) analysis. The BamHI generated RFPs were found to be distinguishable, thus confirming RFP analysis...

  6. Fatal elephant endotheliotropic herpesvirus-1 and -4 co-infection in a juvenile Asian elephant in Europe

    DEFF Research Database (Denmark)

    Seilern-Moy, Katharina; Bertelsen, Mads Frost; Leifsson, Páll S.

    2016-01-01

    Introduction Elephant endotheliotropic herpesvirus-1 (EEHV-1) is one of the major causes of fatality in juvenile Asian elephants (Elephas maximus). On occasions, other EEHV genotypes, i.e. EEHV-3, -4 and -5, have also been reported as the cause of Asian elephant deaths. In this case report we...

  7. Structural map of Kaposi sarcoma-associated herpesvirus RNA provides clues to molecular interactions | Center for Cancer Research

    Science.gov (United States)

    Scientists from CCR have generated a comprehensive structural map of Kaposi sarcoma-associated herpesvirus polyadenylated nuclear (PAN) RNA, a long non-coding RNA that helps the virus evade detection by its host’s immune system. The findings open new oppportunites to study the life cycle of this cancer-causing virus.  Learn more...

  8. Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo

    Science.gov (United States)

    Seimon, Tracie A.; Olson, Sarah H.; Lee, Kerry Jo; Rosen, Gail; Ondzie, Alain; Cameron, Kenneth; Reed, Patricia; Anthony, Simon J.; Joly, Damien O.; McAloose, Denise; Lipkin, W. Ian

    2015-01-01

    Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region. PMID:25781992

  9. Tracing the Co-evolutionary History of the Chelonid Fibropapilloma-associated Herpesvirus and Its Host Sea Turtles

    DEFF Research Database (Denmark)

    Alfaro Nuñez, Luis Alonso

    This thesis describes various aspects of marine turtle (Testudines) evolution and tackles a well-described and controversial disease of these animals, fibropapillomatosis (FP), which is believed to be caused by the Chelonid fibropapilloma-associated herpesvirus (CFPHV). A large dataset of samples...

  10. Validation of a sensitive PCR assay for the detection of Chelonid fibropapilloma-associated herpesvirus in latent turtle infections

    DEFF Research Database (Denmark)

    Alfaro Nuñez, Luis Alonso; Gilbert, M Thomas P

    2014-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV) is hypothesized to be the causative agent of fibropapillomatosis, a neoplastic disease in sea turtles, given its consistent detection by PCR in fibropapilloma tumours. CFPHV has also been detected recently by PCR in tissue samples from...

  11. Distinct herpesvirus resistances and immune responses of three gynogenetic clones of gibel carp revealed by comprehensive transcriptomes.

    Science.gov (United States)

    Gao, Fan-Xiang; Wang, Yang; Zhang, Qi-Ya; Mou, Cheng-Yan; Li, Zhi; Deng, Yuan-Sheng; Zhou, Li; Gui, Jian-Fang

    2017-07-24

    Gibel carp is an important aquaculture species in China, and a herpesvirus, called as Carassius auratus herpesvirus (CaHV), has hampered the aquaculture development. Diverse gynogenetic clones of gibel carp have been identified or created, and some of them have been used as aquaculture varieties, but their resistances to herpesvirus and the underlying mechanism remain unknown. To reveal their susceptibility differences, we firstly performed herpesvirus challenge experiments in three gynogenetic clones of gibel carp, including the leading variety clone A + , candidate variety clone F and wild clone H. Three clones showed distinct resistances to CaHV. Moreover, 8772, 8679 and 10,982 differentially expressed unigenes (DEUs) were identified from comparative transcriptomes between diseased individuals and control individuals of clone A + , F and H, respectively. Comprehensive analysis of the shared DEUs in all three clones displayed common defense pathways to the herpesvirus infection, activating IFN system and suppressing complements. KEGG pathway analysis of specifically changed DEUs in respective clones revealed distinct immune responses to the herpesvirus infection. The DEU numbers identified from clone H in KEGG immune-related pathways, such as "chemokine signaling pathway", "Toll-like receptor signaling pathway" and others, were remarkably much more than those from clone A + and F. Several IFN-related genes, including Mx1, viperin, PKR and others, showed higher increases in the resistant clone H than that in the others. IFNphi3, IFI44-like and Gig2 displayed the highest expression in clone F and IRF1 uniquely increased in susceptible clone A + . In contrast to strong immune defense in resistant clone H, susceptible clone A + showed remarkable up-regulation of genes related to apoptosis or death, indicating that clone A + failed to resist virus offensive and evidently induced apoptosis or death. Our study is the first attempt to screen distinct resistances and

  12. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome.

    Science.gov (United States)

    Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with

  13. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

    Science.gov (United States)

    Polizzotto, Mark N.; Uldrick, Thomas S.; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some

  14. Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri

    Directory of Open Access Journals (Sweden)

    Jean-Paul Vernot

    2015-01-01

    Full Text Available The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip, the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts.

  15. Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri.

    Science.gov (United States)

    Vernot, Jean-Paul; Perdomo-Arciniegas, Ana María; Pérez-Quintero, Luis Alberto; Martínez, Diego Fernando

    2015-01-01

    The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts.

  16. Human herpesvirus-8 positive iatrogenic Kaposi's sarcoma in the setting of refractory ulcerative colitis

    OpenAIRE

    Duh, Erica; Fine, Sean

    2017-01-01

    Although Kaposi sarcoma (KS) has been more traditionally considered an AIDS-defining illness, it may also be seen in individuals on immunosuppresive therapy. We report a case of a patient who presented to the hospital in the setting of increasingly refractory ulcerative colitis. Computed tomography scan of the abdomen was consistent with sigmoid diverticulititis and blood cultures were positive for Klebsiella. After a course of antibiotics with resolution of infection, a colonoscopy was perfo...

  17. Transplacental Human Herpesvirus 6 (HHV-6) Congenital Infection Caused by Maternal Chromosomally Integrated Virus

    Science.gov (United States)

    Hall, Caroline Breese; Caserta, Mary T.; Schnabel, Kenneth C.; Shelley, Lynne M.; Carnahan, Jennifer A.; Marino, Andrea S.; Yoo, Christina; Lofthus, Geraldine K.

    2009-01-01

    Congenital HHV-6 infection results from germline passage of chromosomally-integrated HHV-6 (CI-HHV-6) and from transplacental passage of maternal HHV-6 infection (TP-HHV-6). We aimed to determine if CI-HHV-6 could replicate and cause TP-HHV-6 infection. HHV-6 DNA, variant type, and viral loads were determined on samples (cord blood, peripheral blood, saliva, urine, hair) from 6 infants with TP-HHV-6 and on their parents’ hair. No fathers, but all mothers of TP-HHV-6 infants had CI-HHV-6, and the mother's CI-HHV-6 variant was the same variant causing the TP-HHV-6 congenital infection. This suggests the possibility that CI-HHV-6 replicates, and may cause most, possibly all, congenital HHV-6 infections. PMID:20088693

  18. Assessment of Salivary Human Herpesvirus-6 and Immunoglobulin A Levels in Nurses Working Shifts

    Directory of Open Access Journals (Sweden)

    Hirom Fukuda, RN, PhD

    2008-09-01

    Conclusion: Salivary HHV-6 level may be a more sensitive stress marker than salivary IgA or mood for assessing chronic fatigue in nurses working shifts. Improvement to shift assignments using assessment by salivary HHV-6 is required.

  19. Seroprevalence of Human Herpesvirus-8 in HIV-1 Infected and Uninfected Individuals in Cameroon

    Directory of Open Access Journals (Sweden)

    Owen Wood

    2013-09-01

    Full Text Available We evaluated the prevalence of HHV-8 antibodies in 516 plasma samples collected from HIV positive and negative patients from blood banks and urban areas of Cameroon. Among HIV-1 positive samples, HHV-8 seropositivity rate was 61% based on combined reactivity using both ELISA and IFA techniques. HIV negative samples showed 62% seropositivity rate for HHV-8 antibodies. Our results indicate a high HHV-8 prevalence rate in both HIV infected and uninfected individuals in Cameroon.

  20. Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases.

    Science.gov (United States)

    Sultanova, A; Cistjakovs, M; Gravelsina, S; Chapenko, S; Roga, S; Cunskis, E; Nora-Krukle, Z; Groma, V; Ventina, I; Murovska, M

    2017-01-01

    Viral infections frequently have been cited as important environmental factors implicated in the onset of autoimmune thyroiditis (AIT). The aim of this study was to determine the involvement of HHV-6 infection in the development of autoimmune thyroiditis. This study included 45 patients (42 female and 3 male; median age 47.00 IQR 38.50-57.00) with histologically, laboratory, and clinically confirmed autoimmune thyroiditis, as well as 30 autopsied subjects (26 female and 4 male; median age 58.50, IQR 51.50-67.00) without thyroid pathologies and 30 healthy blood donors (25 female and 5 male; median age 33.50, IQR 27.75-44.25) as controls. Results were obtained by applying molecular virology and immunohistochemistry techniques. The presence of persistent HHV-6 infection in AIT patients was significantly higher (p 0.0058) than in the control group (44/45 (98%) vs. 23/30 (77%), respectively). Also, a significantly higher frequency of HHV-6 activation marker (U79/80 mRNA) was found in patients' thyroid gland tissue samples with AIT in comparison with the control group (18/44 (41%) vs. 1/17 (6%), respectively; p 0.0118). The median HHV-6 load was found to be higher in patients with active viral infection than in patients without it (2147, IQR 971-4188 vs. 551, IQR 145-1589 copies/1×10 6 cells; p 0.003). The presence of HHV-6 antigen expression was demonstrated in intrafollicular cellular clusters and immunohistochemistry indicated thyrocytes in the follicle wall. These findings provide evidence of strong HHV-6 infection association with AIT development. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Molecular phylogeny of equine herpesvirus 1 isolates from onager, zebra and Thomson's gazelle.

    Science.gov (United States)

    Ghanem, Y M; Fukushi, H; Ibrahim, E S M; Ohya, K; Yamaguchi, T; Kennedy, M

    2008-01-01

    Viruses related to equine herpesvirus type 1 (EHV-1) were isolated from an aborted fetus of an onager (Equus hemionus) in 1984, an aborted fetus of Grevy's zebra (Equus grevyi) in 1984 and a Thomson's gazelle (Gazella thomsoni) with nonsuppurative encephalitis in 1996, all in the USA. The mother of the onager fetus and the gazelle were kept near plains zebras (Equus burchelli). In phylogenetic trees based on the nucleotide sequences of the genes for glycoproteins B (gB), I (gI), and E (gE), and teguments including ORF8 (UL51), ORF15 (UL45), and ORF68 (US2), the onager, Grevy's zebra and gazelle isolates formed a genetic group that was different from several horse EHV-1 isolates. Within this group, the onager and gazelle isolates were closely related, while the Grevy's zebra isolate was distantly related to these two isolates. The epizootiological origin of the viruses is discussed.

  2. Prevalence of Bovine Herpesvirus-1 in cattle and buffaloes in Punjab

    Directory of Open Access Journals (Sweden)

    Gurpreet Kaur

    2013-12-01

    Full Text Available Aim: The aim of the present study was to identify the prevalence of Bovine Herpesvirus-1 (BHV-1 in cattle and buffaloes in the Punjab using PCR as diagnostic tool. Materials and Methods: A total of 63 samples (Semen- 57, placental cotyledons-1, vaginal secretions-1, foetal stomach contents-1 and tracheal swabs-3 from cattle and buffaloes were processed for identification of BHV-1 using PCR. Results: From January 2007 to December 2010 (Semen- 57, placental cotyledons-1, vaginal secretions-1, foetal stomach contents-1 and tracheal swabs-3 from cattle and buffaloes were collected. The DNA was extracted from a total of 63 samples and subjected to PCR revealed that none of the sample positive for the BHV-1 infection. Conclusion: From the study it was concluded that the farms screened were free from BHV-1 infection. [Vet World 2013; 6(6.000: 343-345

  3. Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

    Directory of Open Access Journals (Sweden)

    Ndibazza Juliet

    2011-09-01

    Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

  4. [Bovine herpesvirus 4 (BoHV-4): general aspects of the biology and status in Argentina].

    Science.gov (United States)

    Morán, Pedro E; Pérez, Sandra E; Odeón, Anselmo C; Verna, Andrea E

    2015-01-01

    Bovine herpesvirus 4 (BoHV-4) has been isolated from cattle with respiratory infections, vulvovaginitis, mastitis, abortions, endometritis and from apparently healthy animals throughout the world. Although it has not yet been established as causal agent of a specific disease entity, it is primarily associated with reproductive disorders of cattle. This virus can infect a wide range of species, either in vivo or in vitro. Two groups of prototype strains were originated from the first isolates: the DN599-type strains (American group) and the Movar-type strains (European group). In Argentina, BoHV-4 was isolated and characterized in 2007 from vaginal discharge samples taken from cows that had aborted. So far, more than 40 isolates, mainly associated with aborting bovine females have been registered in our country. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Endocrine pancreatic insufficiency secondary to chronic herpesvirus pancreatitis in a cockatiel (Nymphicus hollandicus).

    Science.gov (United States)

    Phalen, David N; Falcon, Michelle; Tomaszewski, Elizabeth K

    2007-06-01

    A cockatiel (Nymphicus hollandicus) examined because of weight loss, polydipsia, and polyuria was diagnosed with diabetes mellitus based on the presence of glucosuria and marked hyperglycemia. Medical attempts to manage the diabetes mellitus were unsuccessful, and the bird was euthanatized. Histopathologic examination of the pancreas revealed a chronic active pancreatitis with herpesviral inclusions in many of the pancreatic acinar and duct cells. Psittacid herpesvirus-1 (PsHV-1) DNA was amplified from the lesion by polymerase chain reaction. Sequencing of the amplicon showed it to be the genotype 1 variant, which is most commonly associated with Pacheco's disease, an acute rapidly fatal systemic infection. The findings in this case suggest that the PsHV-1 genotype may also cause a localized disease of the pancreas. Infection with this virus should be considered as a differential diagnosis in birds with pancreatitis with or without diabetes mellitus.

  6. Cyprinid herpesvirus 3: an interesting virus for applied and fundamental research

    Science.gov (United States)

    2013-01-01

    Cyprinid herpesvirus 3 (CyHV-3), a member of the family Alloherpesviridae is the causative agent of a lethal, highly contagious and notifiable disease in common and koi carp. The economic importance of common and koi carp industries together with the rapid spread of CyHV-3 worldwide, explain why this virus became soon after its isolation in the 1990s a subject of applied research. In addition to its economic importance, an increasing number of fundamental studies demonstrated that CyHV-3 is an original and interesting subject for fundamental research. In this review, we summarized recent advances in CyHV-3 research with a special interest for studies related to host-virus interactions. PMID:24073814

  7. Proteomic and Functional Analyses of the Virion Transmembrane Proteome of Cyprinid Herpesvirus 3.

    Science.gov (United States)

    Vancsok, Catherine; Peñaranda, M Michelle D; Raj, V Stalin; Leroy, Baptiste; Jazowiecka-Rakus, Joanna; Boutier, Maxime; Gao, Yuan; Wilkie, Gavin S; Suárez, Nicolás M; Wattiez, Ruddy; Gillet, Laurent; Davison, Andrew J; Vanderplasschen, Alain F C

    2017-11-01

    Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (open reading frame 32 [ORF32], ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are nonessential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the nonessential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro , and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Δ56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Δ56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25-deleted virus was reduced in intensity and duration to levels similar to those observed for the Δ56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs. IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the

  8. A protective effect of epidermal powder immunization in a mouse model of equine herpesvirus-1 infection

    International Nuclear Information System (INIS)

    Kondo, Takashi; McGregor, Martha; Chu, Qili; Chen, Dexiang; Horimoto, Taisuke; Kawaoka, Yoshihiro

    2004-01-01

    To evaluate the protective effect of epidermal powder immunization (EPI) against equine herpesvirus-1 (EHV-1) infection, we prepared a powder vaccine in which formalin-inactivated virions were embedded in water-soluble, sugar-based particles. A PowderJect device was used to immunize mice with the powder vaccine via their abdominal skin. We found that twice-immunized mice were protected against challenge with the wild-type virus. This protective effect was equivalent to or better than that observed in mice immunized with other types of vaccines, including a gene gun-mediated DNA vaccine containing the glycoprotein D (gD) gene or conventional inactivated virus vaccines introduced via intramuscular or intranasal injections. These findings indicate that the powder vaccine is a promising approach for the immunological control of EHV-1 infection, either alone or as a part of prime-boost vaccination strategies

  9. CLINICAL INFECTION OF TWO CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

    Science.gov (United States)

    Fuery, Angela; Tan, Jie; Peng, RongSheng; Flanagan, Joseph P; Tocidlowski, Maryanne E; Howard, Lauren L; Ling, Paul D

    2016-03-01

    The ability of prior infection from one elephant endotheliotropic herpesvirus (EEHV) type to protect against clinical or lethal infection from others remains an important question. This report describes viremia and subsequent shedding of EEHV1B in two juvenile 4-yr-old Asian elephants within 3 wk or 2 mo following significant infections caused by the rarely seen EEHV4. High levels of EEHV1B shedding were detected in the first elephant prior to emergence of infection and viremia in the second animal. The EEHV1B virus associated with both infections was identical to the strain causing infection in two herd mates previously. High EEHV viremia correlated with leukopenia and thrombocytopenia, which was followed by leukocytosis and thrombocytosis when clinical signs started to resolve. The observations from these cases should be beneficial for helping other institutions monitor and treat elephants infected with EEHV1, the most common virus associated with lethal hemorrhagic disease.

  10. Comparison of genomes of malignant catarrhal fever-associated herpesviruses by restriction endonuclease analysis.

    Science.gov (United States)

    Shih, L M; Zee, Y C; Castro, A E

    1989-01-01

    The restriction endonuclease DNA cleavage patterns of eight isolates of malignant catarrhal fever-associated herpesviruses were examined using the restriction endonucleases HindIII and EcoRI. The eight viruses could be assigned to two distinct groups. Virus isolates from a blue wildebeest, a sika deer and an ibex had restriction endonuclease DNA cleavage patterns that were in general similar to each other. The restriction pattern of these three viruses was distinct from the other five. Of these five, four were isolated from a greater kudu, a white tailed wildebeest, a white bearded wildebeest, and a cape hartebeest. The fifth isolate C500, was isolated from a domestic cow with malignant catarrhal fever. These five viruses had similar DNA cleavage patterns.

  11. ISOLASI KOI HERPESVIRUS (KHV DARI BEBERAPA ORGAN TARGET DENGAN MENGGUNAKAN KULTUR SEL KT-2

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    Tuti Sumiati

    2012-04-01

    Full Text Available Kasus kematian massal pada ikan mas dan koi (Cyprinus carpio yang disebabkan oleh koi herpesvirus (KHV terjadi sejak tahun 2002 dan masih berlangsung hingga sekarang. Pemilihan sampel yang tepat sangat penting untuk mendeteksi dan mengidentifikasi penyakit KHV tersebut. Tujuan dari penelitian ini adalah untuk mengetahui jaringan yang menjadi target infeksi KHV dengan cara isolasi virus menggunakan kultur sel KT-2. Kultur sel diinokulasi dengan ekstrak jaringan organ target (otak, mata, insang, ginjal, limfa, hati, jantung, dan usus, serta gabungan insang, ginjal, dan limfa dan diinkubasi pada suhu 25oC selama 14 hari. Kerusakan sel terjadi pada kultur sel yang diinokulasi dengan ekstrak dari jaringan insang, ginjal dan gabungan organ insang, ginjal, dan limfa. Uji PCR dari media kultur dan sel yang mengalami CPE menunjukkan bahwa CPE disebabkan oleh KHV.

  12. Structural similarities in DNA packaging and delivery apparatuses in Herpesvirus and dsDNA bacteriophages.

    Science.gov (United States)

    Rixon, Frazer J; Schmid, Michael F

    2014-04-01

    Structural information can inform our understanding of virus origins and evolution. The herpesviruses and tailed bacteriophages constitute two large families of dsDNA viruses which infect vertebrates and prokaryotes respectively. A relationship between these disparate groups was initially suggested by similarities in their capsid assembly and DNA packaging strategies. This relationship has now been confirmed by a range of studies that have revealed common structural features in their capsid proteins, and similar organizations and sequence conservation in their DNA packaging machinery and maturational proteases. This concentration of conserved traits in proteins involved in essential and primordial capsid/packaging functions is evidence that these structures are derived from an ancient, common ancestor and is in sharp contrast to the lack of such evidence for other virus functions. Copyright © 2014. Published by Elsevier B.V.

  13. Isolation and characterisation of a ruminant alphaherpesvirus closely related to bovine herpesvirus 1 in a free-ranging red deer

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    Belák Sándor

    2007-09-01

    Full Text Available Abstract Background The genus Varicellovirus of the Herpesviridae subfamily Alphaherpesvirinae includes a cluster of viruses antigenically and genetically related to bovine herpesvirus 1 (BoHV-1: namely bovine herpesvirus 5 (BoHV-5, bubaline herpesvirus 1 (BuHV-1, caprine herpesvirus 1 (CpHV-1, cervid herpesviruses 1 (CvHV-1 and 2 (CvHV-2 and elk herpesvirus 1 (ElkHV-1. Considering the serological relationship between these ruminant alphaherpesviruses, several surveys have studied the occurrence of BoHV-1 related virus infection in wild and domestic ruminant species. In this way, a recent investigation has indicated, in Belgium, a high increase in the serological prevalence of BoHV-1 related virus infection in free-ranging red deer population. In this context, it has been decided to investigate the presence of an alphaherpesvirus spreading in the Belgian free-ranging red deer population. Results The current study reports the first isolation in a free-ranging red deer of a BoHV-1 closely related virus. The isolate was antigenically, genomically and genetically characterised by comparison with several ruminant alphaherpesvirus. Immunofluorescence assays revealed the isolate was antigenically distinct from bovine and caprine alphaherpesviruses. Similarly, BamHI and BstEII restriction analyses demonstrated the genomic difference between the isolate and the other ruminant alphaherpesviruses. Next, the sequencing of selected parts of UL27 and US8 genes showed a high degree of homologies between each BoHV-1 related ruminant alphaherpesvirus and the isolate. Besides the close relationship between all ruminant alphaherpesviruses, the phylogenetic analysis revealed that the isolate clustered with CvHV-1. Conclusion The first isolation of a virus closely related to BoHV-1 in a free-ranging red deer is reported. Data demonstrate that a CvHV-1 strain, named Anlier, circulates in wild red deer in continental Europe. Anlier strain show consistent differences

  14. Efficacy of DNA vaccine encoding koi herpesvirus glycoprotein GP-25in common carp juvenile by immersion

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    Soko Nuswantoro

    2013-11-01

    Full Text Available Koi herpesvirus (KHV is a herpesvirus that particularly infects and causes mass mortality to koi and common carp. Therefore, the protection of common carp from KHV infection is urgently needed. In this study, we developed an application of DNA vaccine encoding KHV glycoprotein-25 by immersion method to increase survival of common carp against KHV infection. A total of 400 common carp juveniles at 30-day-old were immersed in 1-L water containing 1.3×108CFU/mL of the killed Escherichia coli cells carrying DNA vaccine. Three frequencies and three duration of fish immersion were tested, namely: 1×30 minutes, 1×60 minutes, 1× 90 minutes, 2×90 minutes and 3×90 minutes by interval of 24 hours. Reversetranscription polymerase chain reaction analysis showed that DNA vaccine was successfully expressed in the vaccinated fish. Fish at twenty eight days post vaccination were challenged by injecting 10-4 mL of KHV per fish. The result showed that vaccination by 1×30 minutes immersion allowed 61% of fish survived, and this was significantly higher (p<0.05 compared to control (without vaccination, but it was similar among vaccination treatments (p>0.05. The relative percent survival of vaccinated fish were also similar among treatments (p>0.05. DNA vaccination has increased fish survival about two fold higher compared to unvaccinated fish control (26.67%. Thus, DNA vaccination was effectively delivered by immersion for 1×30 minutes, and this technique can be useful to level up the resistance of common carp juveniles against KHV infection. Keywords: DNA vaccine, KHV, glycoprotein, immersion, common carp

  15. The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

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    Thomas Günther

    Full Text Available Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent infection with Kaposi Sarcoma-associated herpesvirus (KSHV, the etiologic agent of Kaposi Sarcoma and primary effusion lymphoma (PEL. By use of high resolution tiling microarrays in conjunction with immunoprecipitation of methylated DNA (MeDIP or modified histones (chromatin IP, ChIP, our study revealed highly distinct landscapes of epigenetic modifications associated with latent KSHV infection in several tumor-derived cell lines as well as de novo infected endothelial cells. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolve slowly and thus are unlikely to control early latency. In contrast, we observed that latency-specific histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, as H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks. Our findings suggest that the modification patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced.

  16. Critical role of the lipid rafts in caprine herpesvirus type 1 infection in vitro.

    Science.gov (United States)

    Pratelli, Annamaria; Colao, Valeriana

    2016-01-04

    The fusion machinery for herpesvirus entry in the host cells involves the interactions of viral glycoproteins with cellular receptors, although additional viral and cellular domains are required. Extensive areas of the plasma membrane surface consist of lipid rafts organized into cholesterol-rich microdomains involved in signal transduction, protein sorting, membrane transport and in many processes of viruses infection. Because of the extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to the lipid rafts, we investigated the effect of cholesterol depletion by methyl-β-cyclodextrin (MβCD) on caprine herpesvirus 1 (CpHV.1) in three important phases of virus infection such as binding, entry and post-entry. MβCD treatment did not prejudice virus binding to cells, while a dose-dependent reduction of the virus yield was observed at the virus entry stage, and 30 mM MβCD reduced infectivity evidently. Treatment of MDBK after virus entry revealed a moderate inhibitory effect suggesting that cholesterol is mainly required during virus entry rather than during the post-entry stage. Alteration of the envelope lipid composition affected virus entry and a noticeable reduction in virus infectivity was detected in the presence of 15 mM MβCD. Considering that the recognition of a host cell receptor is a crucial step in the start-up phase of infection, these data are essential for the study of CpHV.1 pathogenesis. To date virus receptors for CpHV.1 have not yet been identified and further investigations are required to state that MβCD treatment affects the expression of the viral receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Diagnostic validation of three test methods for detection of cyprinid herpesvirus 3 (CyHV-3).

    Science.gov (United States)

    Clouthier, Sharon C; McClure, Carol; Schroeder, Tamara; Desai, Megan; Hawley, Laura; Khatkar, Sunita; Lindsay, Melissa; Lowe, Geoff; Richard, Jon; Anderson, Eric D

    2017-03-06

    Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of koi herpesvirus disease in koi and common carp. The disease is notifiable to the World Organisation for Animal Health. Three tests-quantitative polymerase chain reaction (qPCR), conventional PCR (cPCR) and virus isolation by cell culture (VI)-were validated to assess their fitness as diagnostic tools for detection of CyHV-3. Test performance metrics of diagnostic accuracy were sensitivity (DSe) and specificity (DSp). Repeatability and reproducibility were measured to assess diagnostic precision. Estimates of test accuracy, in the absence of a gold standard reference test, were generated using latent class models. Test samples originated from wild common carp naturally exposed to CyHV-3 or domesticated koi either virus free or experimentally infected with the virus. Three laboratories in Canada participated in the precision study. Moderate to high repeatability (81 to 99%) and reproducibility (72 to 97%) were observed for the qPCR and cPCR tests. The lack of agreement observed between some of the PCR test pair results was attributed to cross-contamination of samples with CyHV-3 nucleic acid. Accuracy estimates for the PCR tests were 99% for DSe and 93% for DSp. Poor precision was observed for the VI test (4 to 95%). Accuracy estimates for VI/qPCR were 90% for DSe and 88% for DSp. Collectively, the results show that the CyHV-3 qPCR test is a suitable tool for surveillance, presumptive diagnosis and certification of individuals or populations as CyHV-3 free.

  18. Development of a quantitative PCR assay for measurement of trichechid herpesvirus 1 load in the Florida manatee ( Trichechus manatus latirostris).

    Science.gov (United States)

    Ferrante, Jason A; Cortés-Hinojosa, Galaxia; Archer, Linda L; Wellehan, James F X

    2017-07-01

    Trichechid herpesvirus 1 (TrHV-1) is currently the only known herpesvirus in any sirenian. We hypothesized that stress may lead to recrudescence of TrHV-1 in manatees, thus making TrHV-1 a potential biomarker of stress. We optimized and validated a TrHV-1 real-time quantitative probe hybridization PCR (qPCR) assay that was used to quantify TrHV-1 in manatee peripheral blood mononuclear cells (PBMCs). Average baseline TrHV-1 loads in a clinically healthy wild Florida manatee ( Trichechus manatus latirostris) population ( n = 42) were 40.9 ± SD 21.2 copies/100 ng DNA; 19 of 42 manatees were positive. TrHV-1 loads were significantly different between the 2 field seasons ( p < 0.025). This optimized and validated qPCR assay may be used as a tool for further research into TrHV-1 in Florida manatees.

  19. THE ROLE OF HERPESVIRUS IN THE PARADIGM OF INFECTIOUS MYOCARDITIS (REVIEW

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    Peremot S.

    2016-03-01

    Full Text Available According to the research of the last decade, there has been growth in the noncoronary disease infarction, increased their share among the causes temporary or persistent disability, disability and deaths. Among others myocarditis, which constitute 11% of all diseases of the cardiovascular system and is responsible for almost 20% of cases of sudden death in people physically safe. The disease is an inflammatory damage to cardiomyocytes, which is caused by direct action or indirectly through immune mechanisms of infectious agents of bacterial, viral, protozoan nature, as well as chemical and physical factors. The term "myocarditis" was first proposed I F Soberheim in 1837 and in 1900. A. Fiedler described the myocardial injury and justified the very concept of primary myocarditis. It is widely accepted that myocarditis - natural complications of infectious diseases in which etiological factor may be any infectious agent. However, at the present stage bacterial pathogens give way to viral. Those viruses according to numerous studies result in the development of myocarditis and consequently lead to the development of myocardial dysfunction. Until recently, most were considered cardiotropic ECHO viruses, Coxsackie group A, B, causing half of all cases of viral myocarditis. However recently reviewed the role of enteroviruses in favor of persistent virus and particularly the family Herpesviridae. The significance in the etiology of myocarditis herpes simplex virus, human herpes type 6, Epstein - Barr virus, cytomegalovirus. Published data indicate that the development of viral myocarditis patients after serous meningoencephalitis caused by the varicella-zoster virus. Widespread herpesvirus diseases their tropism for endothelial cells and myocardium, the capacity for long-term persistence in the body the opportunity to explain virus inducted inflammatory damage to cardiomyocytes. Increased attention to this issue recently linked with the present stage

  20. ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 5, A NEWLY RECOGNIZED ELEPHANT HERPESVIRUS ASSOCIATED WITH CLINICAL AND SUBCLINICAL INFECTIONS IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS)

    Science.gov (United States)

    Atkins, Lisa; Zong, Jian-Chao; Tan, Jie; Mejia, Alicia; Heaggans, Sarah Y.; Nofs, Sally A.; Stanton, Jeffrey J.; Flanagan, Joseph P.; Howard, Lauren; Latimer, Erin; Stevens, Martina R.; Hoffman, Daryl S.; Hayward, Gary S.; Ling, Paul D.

    2013-01-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause acute hemorrhagic disease with high mortality rates in Asian elephants (Elephas maximus). Recently, a new EEHV type known as EEHV5 has been described, but its prevalence and clinical significance remain unknown. In this report, an outbreak of EEHV5 infection in a herd of captive Asian elephants in a zoo was characterized. In February 2011, a 42-yr-old wild-born female Asian elephant presented with bilaterally swollen temporal glands, oral mucosal hyperemia, vesicles on the tongue, and generalized lethargy. The elephant had a leukopenia and thrombocytopenia. She was treated with flunixin meglumine, famciclovir, and fluids. Clinical signs of illness resolved gradually over 2 wk, and the white blood cell count and platelets rebounded to higher-than-normal values. EEHV5 viremia was detectable starting 1 wk before presentation and peaked at the onset of clinical illness. EEHV5 shedding in trunk secretions peaked after viremia resolved and continued for more than 2 mo. EEHV5 trunk shedding from a female herd mate without any detectable viremia was detected prior to onset of clinical disease in the 42-yr-old elephant, indicating reactivation rather than primary infection in this elephant. Subsequent EEHV5 viremia and trunk shedding was documented in the other five elephants in the herd, who remained asymptomatic, except for 1 day of temporal gland swelling in an otherwise-healthy 1-yr-old calf. Unexpectedly, the two elephants most recently introduced into the herd 40 mo previously shed a distinctive EEHV5 strain from that seen in the other five elephants. This is the first report to document the kinetics of EEHV5 infection in captive Asian elephants and to provide evidence that this virus can cause illness in some animals. PMID:23505714

  1. Cloning of the koi herpesvirus (KHV gene encoding thymidine kinase and its use for a highly sensitive PCR based diagnosis

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    Gilad Oren

    2005-03-01

    Full Text Available Abstract Background Outbreaks with mass mortality among common carp Cyprinus carpio carpio and koi Cyprinus carpio koi have occurred worldwide since 1998. The herpes-like virus isolated from diseased fish is different from Herpesvirus cyprini and channel catfish virus and was accordingly designated koi herpesvirus (KHV. Diagnosis of KHV infection based on viral isolation and current PCR assays has a limited sensitivity and therefore new tools for the diagnosis of KHV infections are necessary. Results A robust and sensitive PCR assay based on a defined gene sequence of KHV was developed to improve the diagnosis of KHV infection. From a KHV genomic library, a hypothetical thymidine kinase gene (TK was identified, subcloned and expressed as a recombinant protein. Preliminary characterization of the recombinant TK showed that it has a kinase activity using dTTP but not dCTP as a substrate. A PCR assay based on primers selected from the defined DNA sequence of the TK gene was developed and resulted in a 409 bp amplified fragment. The TK based PCR assay did not amplify the DNAs of other fish herpesviruses such as Herpesvirus cyprini (CHV and the channel catfish virus (CCV. The TK based PCR assay was specific for the detection of KHV and was able to detect as little as 10 fentograms of KHV DNA corresponding to 30 virions. The TK based PCR was compared to previously described PCR assays and to viral culture in diseased fish and was shown to be the most sensitive method of diagnosis of KHV infection. Conclusion The TK based PCR assay developed in this work was shown to be specific for the detection of KHV. The TK based PCR assay was more sensitive for the detection of KHV than previously described PCR assays; it was as sensitive as virus isolation which is the golden standard method for KHV diagnosis and was able to detect as little as 10 fentograms of KHV DNA corresponding to 30 virions.

  2. Isolation and characterization of the genes for two small RNAs of herpesvirus papio and their comparison with Epstein-Barr virus-encoded EBER RNAs.

    Science.gov (United States)

    Howe, J G; Shu, M D

    1988-08-01

    Genes for the Epstein-Barr virus-encoded RNAs (EBERs), two low-molecular-weight RNAs encoded by the human gammaherpesvirus Epstein-Barr virus (EBV), hybridize to two small RNAs in a baboon cell line that contains a similar virus, herpesvirus papio (HVP). The genes for the HVP RNAs (HVP-1 and HVP-2) are located together in the small unique region at the left end of the viral genome and are transcribed by RNA polymerase III in a rightward direction, similar to the EBERs. There is significant similarity between EBER1 and HVP-1 RNA, except for an insert of 22 nucleotides which increases the length of HVP-1 RNA to 190 nucleotides. There is less similarity between the sequences of EBER2 and HVP-2 RNA, but both have a length of about 170 nucleotides. The predicted secondary structure of each HVP RNA is remarkably similar to that of the respective EBER, implying that the secondary structures are important for function. Upstream from the initiation sites of all four RNA genes are several highly conserved sequences which may function in the regulation of transcription. The HVP RNAs, together with the EBERs, are highly abundant in transformed cells and are efficiently bound by the cellular La protein.

  3. Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4+ T cell proliferation

    International Nuclear Information System (INIS)

    Liu, Wan; Qin, Yan; Bai, Lei; Lan, Ke; Wang, Jian-Hua

    2013-01-01

    Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC–HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4 + T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC–HIV-1 interaction to elucidate HIV/AIDS pathogenesis. - Highlights: ► KSHV impaired the ability of MDDCs to drive proliferation of resting CD4 + T cells. ► KSHV stimulation matured MDDCs and enhanced HIV-1 endocytosis. ► KSHV stimulated MDDCs increased ICAM-1 expression and tighten contact with T cells. ► KSHV-stimulated MDDCs promoted HIV-1 trans-infection of CD4 + T cells

  4. Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4{sup +} T cell proliferation

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    Liu, Wan; Qin, Yan; Bai, Lei [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Graduate School of the Chinese Academy of Sciences, Beijing (China); Lan, Ke [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Wang, Jian-Hua, E-mail: Jh_wang@sibs.ac.cn [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China)

    2013-06-05

    Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC–HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC–HIV-1 interaction to elucidate HIV/AIDS pathogenesis. - Highlights: ► KSHV impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells. ► KSHV stimulation matured MDDCs and enhanced HIV-1 endocytosis. ► KSHV stimulated MDDCs increased ICAM-1 expression and tighten contact with T cells. ► KSHV-stimulated MDDCs promoted HIV-1 trans-infection of CD4{sup +} T cells.

  5. Dual transcriptomics of virus-host interactions: comparing two Pacific oyster families presenting contrasted susceptibility to ostreid herpesvirus 1.

    Science.gov (United States)

    Segarra, Amélie; Mauduit, Florian; Faury, Nicole; Trancart, Suzanne; Dégremont, Lionel; Tourbiez, Delphine; Haffner, Philippe; Barbosa-Solomieu, Valérie; Pépin, Jean-François; Travers, Marie-Agnès; Renault, Tristan

    2014-07-09

    Massive mortality outbreaks affecting Pacific oyster (Crassostrea gigas) spat in various countries have been associated with the detection of a herpesvirus called ostreid herpesvirus type 1 (OsHV-1). However, few studies have been performed to understand and follow viral gene expression, as it has been done in vertebrate herpesviruses. In this work, experimental infection trials of C. gigas spat with OsHV-1 were conducted in order to test the susceptibility of several bi-parental oyster families to this virus and to analyze host-pathogen interactions using in vivo transcriptomic approaches. The divergent response of these oyster families in terms of mortality confirmed that susceptibility to OsHV-1 infection has a significant genetic component. Two families with contrasted survival rates were selected. A total of 39 viral genes and five host genes were monitored by real-time PCR. Initial results provided information on (i) the virus cycle of OsHV-1 based on the kinetics of viral DNA replication and transcription and (ii) host defense mechanisms against the virus. In the two selected families, the detected amounts of viral DNA and RNA were significantly different. This result suggests that Pacific oysters are genetically diverse in terms of their susceptibility to OsHV-1 infection. This contrasted susceptibility was associated with dissimilar host gene expression profiles. Moreover, the present study showed a positive correlation between viral DNA amounts and the level of expression of selected oyster genes.

  6. Serologic and molecular evidence for testudinid herpesvirus 2 infection in wild Agassiz’s desert tortoise, Gopherus agassizii

    Science.gov (United States)

    Jacobson, Elliott R.; Berry, Kristin H.; Wellehan, James F. X.; Origgi, Francesco; Childress, April L.; Braun, Josephine; Schrenzel, Mark; Yee, Julie; Rideout, Bruce

    2012-01-01

    Following field observations of wild Agassiz’s desert tortoises (Gopherus agassizii) with oral lesions similar to those seen in captive tortoises with herpesvirus infection, we measured the prevalence of antibodies to Testudinid herpesvirus (TeHV) 3 in wild populations of desert tortoises in California. The survey revealed 30.9% antibody prevalence. In 2009 and 2010, two wild adult male desert tortoises, with gross lesions consistent with trauma and puncture wounds, respectively, were necropsied. Tortoise 1 was from the central Mojave Desert and tortoise 2 was from the northeastern Mojave Desert. We extracted DNA from the tongue of tortoise 1 and from the tongue and nasal mucosa of tortoise 2. Sequencing of polymerase chain reaction products of the herpesviral DNA-dependent DNA polymerase gene and the UL39 gene respectively showed 100% nucleotide identity with TeHV2, which was previously detected in an ill captive desert tortoise in California. Although several cases of herpesvirus infection have been described in captive desert tortoises, our findings represent the first conclusive molecular evidence of TeHV2 infection in wild desert tortoises. The serologic findings support cross-reactivity between TeHV2 and TeHV3. Further studies to determine the ecology, prevalence, and clinical significance of this virus in tortoise populations are needed.

  7. Mutations in the C-terminal region affect subcellular localization of crucian carp herpesvirus (CaHV) GPCR.

    Science.gov (United States)

    Wang, Jun; Gui, Lang; Chen, Zong-Yan; Zhang, Qi-Ya

    2016-08-01

    G protein-coupled receptors (GPCRs) are known as seven transmembrane domain receptors and consequently can mediate diverse biological functions via regulation of their subcellular localization. Crucian carp herpesvirus (CaHV) was recently isolated from infected fish with acute gill hemorrhage. CaHV GPCR of 349 amino acids (aa) was identified based on amino acid identity. A series of variants with truncation/deletion/substitution mutation in the C-terminal (aa 315-349) were constructed and expressed in fathead minnow (FHM) cells. The roles of three key C-terminal regions in subcellular localization of CaHV GPCR were determined. Lysine-315 (K-315) directed the aggregation of the protein preferentially at the nuclear side. Predicted N-myristoylation site (GGGWTR, aa 335-340) was responsible for punctate distribution in periplasm or throughout the cytoplasm. Predicted phosphorylation site (SSR, aa 327-329) and GGGWTR together determined the punctate distribution in cytoplasm. Detection of organelles localization by specific markers showed that the protein retaining K-315 colocalized with the Golgi apparatus. These experiments provided first evidence that different mutations of CaHV GPCR C-terminals have different affects on the subcellular localization of fish herpesvirus-encoded GPCRs. The study provided valuable information and new insights into the precise interactions between herpesvirus and fish cells, and could also provide useful targets for antiviral agents in aquaculture.

  8. A Promising Recombinant Herpesvirus of Turkeys Vaccine Expressing PmpD-N of Chlamydia psittaci Based on Elongation Factor-1 Alpha Promoter

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    Shanshan Liu

    2017-12-01

    Full Text Available The obligate intracellular Gram-negative bacterium Chlamydia psittaci often causes avian chlamydiosis and influenza-like symptoms in humans. However, the commercial subunit C. psittaci vaccine could only provide a partial protection against avian chlamydiosis due to poor cellular immune response. In our previous study, a recombinant herpesvirus of turkeys (HVT-delivered vaccine against C. psittaci and Marek’s disease based on human cytomegalovirus (CMV promoter (rHVT-CMV-pmpD was developed and provided an effective protection against C. psittaci disease with less lesions and reduced chlamydial loads. In this study, we developed another recombinant HVT vaccine expressing the N-terminal fragment of PmpD (PmpD-N based on human elongation factor-1 alpha (EF-1α promoter (rHVT-EF-pmpD by modifying the HVT genome within a bacterial artificial chromosome. The related characterization of rHVT-EF-pmpD was evaluated in vitro in comparison with that of rHVT-CMV-pmpD. The expression of PmpD-N was determined by western blot. Under immunofluorescence microscopy, PmpD-N protein of both two recombinant viruses was located in the cytoplasm and on the cell surface. Growth kinetics of rHVT-EF-pmpD was comparable to that of rHVT-CMV-pmpD, and the growth rate of rHVT-EF-pmpD was apparently higher than that of rHVT-CMV-pmpD on 48, 72, and 120 h postinfection. Macrophages activated by rHVT-EF-pmpD could produce more nitric oxide and IL-6 than that activated by rHVT-CMV-pmpD. In this study, a recombinant HVT vaccine expressing PmpD-N based on EF-1α promoter was constructed successfully, and a further research in vivo was needed to analyze the vaccine efficacy.

  9. Global distribution of Chelonid fibropapilloma-associated herpesvirus among clinically healthy sea turtles.

    Science.gov (United States)

    Alfaro-Núñez, Alonzo; Frost Bertelsen, Mads; Bojesen, Anders Miki; Rasmussen, Isabel; Zepeda-Mendoza, Lisandra; Tange Olsen, Morten; Gilbert, Marcus Thomas Pius

    2014-10-25

    Fibropapillomatosis (FP) is a neoplastic disease characterized by cutaneous tumours that has been documented to infect all sea turtle species. Chelonid fibropapilloma-associated herpesvirus (CFPHV) is believed to be the aetiological agent of FP, based principally on consistent PCR-based detection of herpesvirus DNA sequences from FP tumours. We used a recently described PCR-based assay that targets 3 conserved CFPHV genes, to survey 208 green turtles (Chelonia mydas). This included both FP tumour exhibiting and clinically healthy individuals. An additional 129 globally distributed clinically healthy individual sea turtles; representing four other species were also screened. CFPHV DNA sequences were obtained from 37/37 (100%) FP exhibiting green turtles, and 45/300 (15%) clinically healthy animals spanning all five species. Although the frequency of infected individuals per turtle population varied considerably, most global populations contained at least one CFPHV positive individual, with the exception of various turtle species from the Arabian Gulf, Northern Indian Ocean and Puerto Rico. Haplotype analysis of the different gene markers clustered the CFPHV DNA sequences for two of the markers (UL18 and UL22) in turtles from Turks and Caicos separate to all others, regardless of host species or geographic origin. Presence of CFPHV DNA within globally distributed samples for all five species of sea turtle was confirmed. While 100% of the FP exhibiting green turtles yielded CFPHV sequences, surprisingly, so did 15% of the clinically healthy turtles. We hypothesize that turtle populations with zero (0%) CFPHV frequency may be attributed to possible environmental differences, diet and/or genetic resistance in these individuals. Our results provide first data on the prevalence of CFPHV among seemingly healthy turtles; a factor that may not be directly correlated to the disease incidence, but may suggest of a long-term co-evolutionary latent infection interaction between

  10. Quantitative molecular viral loads in 7 horses with naturally occurring equine herpesvirus-1 infection.

    Science.gov (United States)

    Estell, K E; Dawson, D R; Magdesian, K G; Swain, E; Laing, S T; Siso, S; Mapes, S; Pusterla, N

    2015-11-01

    Data associating quantitative viral load with severity, clinical signs and survival in equine herpesvirus-1 myeloencephalopathy (EHM) have not been reported. To report the clinical signs, treatment, and temporal progression of viral loads in 7 horses with naturally occurring EHM and to examine the association of these factors with survival. Retrospective case series. The population included 7 horses with EHM presented to the University of California, Davis William R. Pritchard Veterinary Medical Teaching Hospital from May to September 2011. Horses were graded using a neurological grading scale. Daily quantitative PCR was performed on nasal secretions and whole blood. Treatment, survival, outcome and histopathology were reported. At presentation, one horse was neurological grade 5/5, 3 were grade 4/5 and 3 were grade 3/5. All were treated with anti-inflammatory drugs, valacyclovir and management in a sling if necessary. All were infected with equine herpesvirus-1 of DNA polymerase D752 genotype. Peak viral load in nasal secretions and blood of 5 survivors ranged from 6.9 × 10(3) to 2.81 × 10(5) (median 5.11 × 10(4) ) and from 143 to 4340 gB gene copies/million eukaryotic cells (median 3146), respectively. The 2 nonsurvivors presented with grade 3/5 neurological signs and progressed to encephalopathy. Peak viral load was higher in nonsurvivors, with levels in nasal secretions of 1.9 × 10(9) and 2.2 × 10(9) and in blood of 2.05 × 10(4) and 1.02 × 10(5) gB gene copies/million eukaryotic cells. Case fatality was 2/7. Nonsurvivors had viral loads 1000-fold higher in nasal secretions and 10-fold higher in blood than survivors. There was no relationship between severity of clinical signs at presentation and survival. Thus, encephalopathy and high viral load were negatively associated with survival in this population. Further research should be performed to determine whether high viral loads are associated with encephalopathy and poor prognosis. The Summary is

  11. Investigations on the presence of antibodies against equine herpesvirus-1 in blood serum of foals, prior to and after colostrum intake

    Directory of Open Access Journals (Sweden)

    Lauš Saša

    2015-01-01

    Full Text Available The titer of specific antibodies against equine herpesvirus-1 in blood serum was tested in two groups of mares and their foals. The first group consisted of 12 mares, Standardbred and Serbian Trotter breed, who were vaccinated against equine herpesvirus-1 and 4 in the 5th, 7th and 9th month of pregnancy. On the contrary, 12 mares from the second group, of Lipizzaner breed, were not vaccinated. The mares’ blood samples for antibodies titer investigation were taken 30, 15 and 7 days before the expected partus, then immediately after the partus, while their foals’ blood samples were taken immediately after foaling, then just before colostrum intake, and finally 1, 2, 3 and 7 days later. The titer of antibodies against equine herpesvirus-1 was tested by the method of virus - neutralization, on microtiter plates with constant dose of the virus and serial double dilutions of the serum. In unvaccinated mares, titer of antibodies against equine herpesvirus-1 was either low or not present, but on the contrary, in the vaccinated ones the antibodies titer ranged from 1:32 to 1:256. In the foals originating from both vaccinated and unvaccinated there were not found specific antibodies in the serum before colostrum intake. After the colostrum intake, the values of specific antibodies against equine herpesvirus-1 significantly increased in the foals originating from the vaccinated mares, and ranged from 1:8 to 1:32.

  12. The porcine lymphotropic herpesvirus 1 encodes functional regulators of gene expression

    International Nuclear Information System (INIS)

    Lindner, I.; Ehlers, B.; Noack, S.; Dural, G.; Yasmum, N.; Bauer, C.; Goltz, M.

    2007-01-01

    The porcine lymphotropic herpesviruses (PLHV) are discussed as possible risk factors in xenotransplantation because of the high prevalence of PLHV-1, PLHV-2 and PLHV-3 in pig populations world-wide and the fact that PLHV-1 has been found to be associated with porcine post-transplant lymphoproliferative disease. To provide structural and functional knowledge on the PLHV immediate-early (IE) transactivator genes, the central regions of the PLHV genomes were characterized by genome walking, sequence and splicing analysis. Three spliced genes were identified (ORF50, ORFA6/BZLF1 h , ORF57) encoding putative IE transactivators, homologous to (i) ORF50 and BRLF1/Rta (ii) K8/K-bZIP and BZLF1/Zta and (iii) ORF57 and BMLF1 of HHV-8 and EBV, respectively. Expressed as myc-tag or HA-tag fusion proteins, they were located to the cellular nucleus. In reporter gene assays, several PLHV-promoters were mainly activated by PLHV-1 ORF50, to a lower level by PLHV-1 ORFA6/BZLF1 h and not by PLHV-1 ORF57. However, the ORF57-encoded protein acted synergistically on ORF50-mediated activation

  13. Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

    Science.gov (United States)

    Bots, S T F; Hoeben, R C

    2017-07-01

    Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require lifelong treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system. Viruses in particular are masters of exploitation and modulation of their hosts immune response. The Herpesviridae family provides a proof of concept for this as these viruses are capable to establish latency and a lifelong persistence in the infected hosts. While several viral proteins involved in immune evasion have been characterized, the Herpesviridae also encode a multitude of viral microRNA (miRNAs). Several of these miRNAs have been demonstrated to reduce the sensitivity of the infected cells to the destructive action of the host's immune cells. In this review, the miRNAs of some common herpesviruses that are associated with immune modulation will be discussed with a focus on their potential use in strategies aiming at generating non-immunogenic cells for transplantation.

  14. Co-occurrence of Mycoplasma Species and Pigeon Herpesvirus-1 Infection in Racing Pigeons ( Columba livia).

    Science.gov (United States)

    Hellebuyck, Tom; Göbel, Stephan; Pasmans, Frank; Adriaensen, Connie; Martel, An

    2017-12-01

    Oropharyngeal swab samples were collected from 438 live racing pigeons ( Columba livia), with and without signs of respiratory disease, that were housed in 220 lofts in 3 provinces in the western part of the Netherlands. Polymerase chain reaction (PCR) was used to identify Mycoplasma species and pigeon herpesvirus-1 (PHV-1) from the samples. In 8.6% of the pigeon lofts tested, signs of respiratory disease were present in pigeons at sampling, and in 30.9% of the sampled pigeon lofts, respiratory signs were observed in pigeons during the 6-month period immediately before sampling. A total of 39.8% of tested pigeons (54.5% of tested lofts) were positive for Mycoplasma species, and 30.6% of tested pigeons (48.6% of tested lofts) were positive for PHV-1. In 15.8% of the tested pigeons (26.8% of tested pigeon lofts), coinfection by Mycoplasma species and PHV-1 was identified. The number of pigeon lofts having pigeons coinfected by Mycoplasma species and PHV-1 was higher than that where only one of the infections was identified. Neither the presence of Mycoplasma species, PHV-1, nor the co-occurrence of both infections was significantly associated with signs of respiratory disease.

  15. Acute and latent infection by bovine herpesvirus type 2 in a guinea pig model.

    Science.gov (United States)

    Torres, Fabrício Dias; Cargnelutti, Juliana Felipetto; Masuda, Eduardo Kenji; Weiblen, Rudi; Flores, Eduardo Furtado

    2010-02-01

    Bovine herpetic mammillits is a self-limiting cutaneous disease of the udder and teats of cows associated with bovine herpesvirus 2 (BoHV-2) whose pathogenesis is poorly understood. This article describes the use of guinea pigs (Cavia porcellus) to study the pathogenesis of BoHV-2 infection. Twelve weanling female guinea pigs inoculated subcutaneously with BoHV-2 in the genitalia and teats developed local hyperemia, edema, vesicles, ulcers and scabs. Infectious virus was recovered between days 3 and 7 post-infection (pi) from the genital area (9/12) and teats (1/12); and all inoculated animals seroconverted (virus-neutralizing titers of 16-128). Histological examination of lesions revealed lymphoplasmacytic perivascular infiltrates and intranuclear inclusion bodies in keratinocytes. PCR examination of tissues collected at day 35 pi detected latent viral DNA predominantly in lumbosacral spinal segments. In another experiment, eight females inoculated with BoHV-2 in the genitalia and treated with dexamethasone (Dx) at day 35 pi developed mild to moderate local signs, yet no virus could be recovered from lesions. PCR examination of spinal segments from these animals confirmed the presence of latent viral DNA. These results demonstrate that guinea pigs are susceptible to BoHV-2 infection and therefore may be used to study selected aspects of BoHV-2 biology.

  16. Ostreid herpesvirus in wild oysters from the Huelva coast (SW Spain).

    Science.gov (United States)

    López-Sanmartín, M; López-Fernández, J R; Cunha, M E; De la Herrán, R; Navas, J I

    2016-08-09

    This is the first report of ostreid herpesvirus 1 microvariant (OsHV-1 µVar) infecting natural oyster beds located in Huelva (SW Spain). The virus was detected in 3 oyster species present in the intertidal zone: Crassostrea gigas (Thunberg, 1793), C. angulata (Lamarck, 1819) and, for the first time, in Ostrea stentina Payraudeau, 1826. Oysters were identified by a specific polymerase chain reaction (PCR) and posterior restriction fragment length polymorphism (RFLP) analysis based on cytochrome oxidase I (COI) mitochondrial DNA. Results confirmed that C. angulata still remains the dominant oyster population in SW Spain despite the introduction of C. gigas for cultivation in the late 1970s, and its subsequent naturalization. C. angulata shows a higher haplotype diversity than C. gigas. OsHV-1 virus was detected by PCR with C2/C6 pair primers. Posterior RFLP analyses with the restriction enzyme MfeI were done in order to reveal the OsHV-1 µVar. Detections were confirmed by DNA sequencing, and infections were evidenced by in situ hybridization in C. gigas, C. angulata and O. stentina samples. The prevalence was similar among the 3 oyster species but varied between sampling locations, being higher in areas with greater harvesting activities. OsHV-1 µVar accounted for 93% of all OsHV-1 detected.

  17. Potential Noncutaneous Sites of Chelonid Herpesvirus 5 Persistence and Shedding in Green Sea Turtles Chelonia mydas.

    Science.gov (United States)

    Page-Karjian, Annie; Gottdenker, Nicole L; Whitfield, Jordyn; Herbst, Lawrence; Norton, Terry M; Ritchie, Branson

    2017-09-01

    Chelonid herpesvirus 5 (ChHV5), the likely etiologic agent of sea turtle fibropapillomatosis (FP), is predicted to be unevenly distributed within an infected turtle, in which productive virus replication and virion shedding occurs in cutaneous tumor keratinocytes. In this study, we measured and compared ChHV5 DNA quantities in tumors, skin, urine, major organs, and nervous tissue samples from green turtles Chelonia mydas. These samples were taken from the carcasses of 10 juvenile green turtles with and without clinical signs of FP that stranded in Florida during 2014. Quantitative PCR for ChHV5 UL30 was used to identify ChHV5 DNA in tumors, skin, heart, kidney, nerves, and urine sampled from five out of five FP-positive and three out of five FP-free turtles. The most frequently co-occurring sites were cutaneous tumor and kidney (n = 4). Novel data presented here include the identification of ChHV5 DNA in kidney, heart, and nerve samples from three FP-free turtles. These data support candidate nontumored anatomic sites of ChHV5 DNA localization and mobilization during two different disease states that may be involved in the ChHV5 infection cycle. Received September 8, 2016; accepted April 17, 2017.

  18. Plasmid origin of replication of herpesvirus papio: DNA sequence and enhancer function.

    Science.gov (United States)

    Loeb, D D; Sung, N S; Pesano, R L; Sexton, C J; Hutchison, C; Pagano, J S

    1990-01-01

    Herpesvirus papio (HVP) is a lymphotropic virus of baboons which is related to Epstein-Barr virus (EBV) and produces latent infection. The nucleotide sequence of the 5,775-base-pair (bp) EcoRI K fragment of HVP, which has previously been shown to confer the ability to replicate autonomously, has been determined. Within this DNA fragment is a region which bears structural and sequence similarity to the ori-P region of EBV. The HVP ori-P region has a 10- by 26-bp tandem array which is related to the 20- by 30-bp tandem array from the EBV ori-P region. In HVP there is an intervening region of 764 bp followed by five partial copies of the 26-bp monomer. Both the EBV and HVP 3' regions have the potential to form dyad structures which, however, differ in arrangement. We also demonstrate that a transcriptional enhancer which requires transactivation by a virus-encoded factor is present in the HVP ori-P. Images PMID:2159548

  19. Cloning ORF2 Membrane Protein of Koi Herpesvirus Lake Toba, Indonesian Isolate

    Directory of Open Access Journals (Sweden)

    MURWANTOKO

    2009-06-01

    Full Text Available Koi herpesvirus (KHV caused significant morbidity and mortality in koi and common carp. KHV which showed strong antigenic property implied that KHV virion or proteins may be used as antigen to raise antibody or vaccine to increase the resistance. The objectives of this research were to (i clone KHV membrane protein ORF2, (ii analysis on immunogenicity, and (iii genetic tracing. Based on genbank data, one pair of primers was designed to amplify KHV ORF2. The KHV ORF2 can be amplified using infected fish DNA which originally from Toba Lake, Sumatera, Indonesia. The KHV ORF2 composed of 699 nucleotides encoded for 292 amino acids. BLAST analysis showed that KHV ORF2 had 100% homology with KHV-J and KHV0301 strains from Japan; 98 and 91% homology on nucleotides and amino acids respectively with both KHV-U strain from Unites State and KHV-I strain from Israel. KHV in Indonesia was most likely to have originated from Japan via spreading directly or not directly to China or Hongkong. Based on T- and B-cell epitopes prediction, membrane protein ORF2 was proposed has a potency to be used in development vaccine and immunodetection.

  20. RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

    Science.gov (United States)

    Viollet, Coralie; Davis, David A.; Tekeste, Shewit S.; Reczko, Martin; Pezzella, Francesco; Ragoussis, Jiannis

    2017-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases. PMID:28046107

  1. Detection and distribution of ostreid herpesvirus 1 in experimentally infected Pacific oyster spat.

    Science.gov (United States)

    Segarra, Amélie; Baillon, Laury; Faury, Nicole; Tourbiez, Delphine; Renault, Tristan

    2016-01-01

    High mortality rates are reported in spat and larvae of Pacific oyster Crassostrea gigas and associated with ostreid herpesvirus 1 (OsHV-1) detection in France. Although the viral infection has been experimentally reproduced in oyster larvae and spat, little knowledge is currently available concerning the viral entry and its distribution in organs and tissues. This study compares OsHV-1 DNA and RNA detection and localization in experimentally infected oysters using two virus doses: a low dose that did not induce any mortality and a high dose inducing high mortality. Real time PCR demonstrated significant differences in terms of viral DNA amounts between the two virus doses. RNA transcripts were detected in oysters receiving the highest dose of viral suspension whereas no transcript was observed in oysters injected with the low dose. This study also allowed observing kinetics of viral DNA and RNA detection in different tissues of oyster spat. Finally, viral detection was significantly different in function of tissues (p<0.005), time (p<0.005) with an interaction between tissues and time (p<0.005) for each probe. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Transcriptomic study of 39 ostreid herpesvirus 1 genes during an experimental infection.

    Science.gov (United States)

    Segarra, Amélie; Faury, Nicole; Pépin, Jean-François; Renault, Tristan

    2014-06-01

    Massive mortality outbreaks have been reported in France since 2008 among Pacific oysters, Crassostrea gigas, with the detection of a particular OsHV-1 variant called μVar. Virus infection can be induced in healthy spat in experimental conditions allowing to better understand the disease process, including viral gene expression. Although gene expression of other herpesviruses has been widely studied, we provide the first study following viral gene expression of OsHV-1 over time. In this context, an in vivo transcriptomic study targeting 39 OsHV-1 genes was carried out during an experimental infection of Pacific oyster spat. For the first time, several OsHV-1 mRNAs were detected by real-time PCR at 0 h, 2 h, 4 h, 18 h, 26 h and 42 h post-injection. Several transcripts were detected at 2h post-infection and at 18 h post-infection for all selected ORFs. Quantification of virus gene expression at different times of infection was also carried out using an oyster housekeeping gene, Elongation factor. Developing an OsHV-1-specific reverse transcriptase real time PCR targeting 39 viral gene appears a new tool in terms of diagnosis and can be used to complement viral DNA detection in order to monitor viral replication. Copyright © 2014. Published by Elsevier Inc.

  3. Construction of an infectious clone of canine herpesvirus genome as a bacterial artificial chromosome.

    Science.gov (United States)

    Arii, Jun; Hushur, Orkash; Kato, Kentaro; Kawaguchi, Yasushi; Tohya, Yukinobu; Akashi, Hiroomi

    2006-04-01

    Canine herpesvirus (CHV) is an attractive candidate not only for use as a recombinant vaccine to protect dogs from a variety of canine pathogens but also as a viral vector for gene therapy in domestic animals. However, developments in this area have been impeded by the complicated techniques used for eukaryotic homologous recombination. To overcome these problems, we used bacterial artificial chromosomes (BACs) to generate infectious BACs. Our findings may be summarized as follows: (i) the CHV genome (pCHV/BAC), in which a BAC flanked by loxP sites was inserted into the thymidine kinase gene, was maintained in Escherichia coli; (ii) transfection of pCHV/BAC into A-72 cells resulted in the production of infectious virus; (iii) the BAC vector sequence was almost perfectly excisable from the genome of the reconstituted virus CHV/BAC by co-infection with CHV/BAC and a recombinant adenovirus that expressed the Cre recombinase; and (iv) a recombinant virus in which the glycoprotein C gene was deleted was generated by lambda recombination followed by Flp recombination, which resulted in a reduction in viral titer compared with that of the wild-type virus. The infectious clone pCHV/BAC is useful for the modification of the CHV genome using bacterial genetics, and CHV/BAC should have multiple applications in the rapid generation of genetically engineered CHV recombinants and the development of CHV vectors for vaccination and gene therapy in domestic animals.

  4. Development of canine herpesvirus based antifertility vaccines for foxes using bacterial artificial chromosomes.

    Science.gov (United States)

    Strive, Tanja; Hardy, Christopher M; French, Nigel; Wright, John D; Nagaraja, Nitin; Reubel, Gerhard H

    2006-02-13

    Using bacterial artificial chromosome (BAC) technology, a canine herpesvirus (CHV)-based recombinant vaccine vector was produced for the development of an antifertility vaccine for foxes. Infectious viruses were recovered following transfection of canid cells with a BAC plasmid carrying the complete CHV genome. In vitro growth characteristics of BAC-derived viruses were similar to that of wildtype (wt)-CHV. Two recombinant antigens, fox zona pellucida protein subunit 3 (fZPC) and enhanced green fluorescent protein (EGFP) as control antigen, were inserted into thymidine kinase (TK) locus of the CHV genome and shown to be efficiently expressed in vitro. Inoculation of foxes with transgenic CHVs induced CHV specific antibodies, but was innocuous and failed to elicit transgene-specific antibody responses. Infectious virus or viral DNA was not detected in mucosal secretions or tissues of vaccinated foxes. The CHV-BAC system proved to be a quick and reliable method to manipulate the CHV genome. It will help to readily apply changes in the vector design in order to improve virus replication in vivo.

  5. Protection of puppies against canine herpesvirus by vaccination of the dams.

    Science.gov (United States)

    Poulet, H; Guigal, P M; Soulier, M; Leroy, V; Fayet, G; Minke, J; Chappuis Merial, G

    2001-06-02

    Six bitches free of canine herpesvirus 1 (CHV-1) were vaccinated against the virus; a first injection was given 10 days after the presumed date of mating and a second six weeks later. Six similar bitches were left unvaccinated as controls, and all the pups were challenged oronasally with a virulent strain of CHV-1 at three days of age. All the vaccinated bitches seroconverted and had high antibody titres when the puppies were challenged, but the control bitches remained seronegative. In the control group, 62 per cent (18 of 29) of the pups died of CHV-1-induced disease; most of them showed typical clinical signs and macroscopic lesions, and CHV-1 infection was confirmed by the isolation of the virus or by PCR. None of the puppies in the vaccinated group died of CHV-1 infection. The efficacy of the vaccine was confirmed in CHV-1-positive breeding units. The rate of pregnancy tended to be higher in vaccinated bitches and the mortality of pups before weaning was significantly reduced in the litters born to vaccinated bitches.

  6. Suitability of canine herpesvirus as a vector for oral bait vaccination of foxes.

    Science.gov (United States)

    Reubel, Gerhard H; Wright, John; Pekin, Jenny; French, Nigel; Strive, Tanja

    2006-05-31

    Studies were conducted to evaluate the feasibility of using canine herpesvirus (CHV) as a vaccine vector for bait-delivered oral vaccination of wild foxes. To test the viability of CHV in baits, CHV was freeze-dried, incorporated into different baits, stored, and the remaining viral infectivity tested in cell culture after varying periods of time at different storage temperatures. Experimental baits (mouse carcasses) and commercial baits (FOXOFF and PROBAIT) were prepared with either liquid or freeze-dried CHV and tested in two fox trials for their capacity to induce CHV-specific antibodies following oral baiting. Freeze-drying and storage temperatures below 0 degrees C had a stabilizing effect to virus infectivity. When stored at -20 degrees C, freeze-dried CHV retained its full infectivity for up to 3 months in PROBAIT baits, the remaining infectivity in FOXOFF baits was 100-fold less. Oral baiting with CHV induced antiviral serum antibodies in all vaccinated foxes (20/20). None of the vaccinated foxes became ill or shed infectious virus into the environment although viral DNA was detected in body secretions as evaluated by PCR. The results indicate that CHV can be freeze-dried and stored over extended periods of time without loosing much of its infectivity. This is the first report of CHV being used for oral bait vaccination of foxes. It appears that CHV is well suited for use as a recombinant vector for wild canids.

  7. A virus vector based on Canine Herpesvirus for vaccine applications in canids.

    Science.gov (United States)

    Strive, T; Hardy, C M; Wright, J; Reubel, G H

    2007-01-31

    Canine Herpesvirus (CHV) is being developed as a virus vector for the vaccination of European red foxes. However, initial studies using recombinant CHV vaccines in foxes revealed viral attenuation and lack of antibody response to inserted foreign antigens. These findings were attributed both to inactivation of the thymidine kinase (TK) gene and excess foreign genetic material in the recombinant viral genome. In this study, we report an improved CHV-bacterial artificial chromosome (BAC) vector system designed to overcome attenuation in foxes. A non-essential region was identified in the CHV genome as an alternative insertion site for foreign genes. Replacement of a guanine/cytosine (GC)-rich intergenic region between UL21 and UL22 of CHV with a marker gene did not change growth behaviour in vitro, showing that this region is not essential for virus growth in cell culture. We subsequently produced a CHV-BAC vector with an intact TK gene in which the bacterial genes and the antigen expression cassette were inserted into this GC-rich locus. Unlike earlier constructs, the new CHV-BAC allowed self-excision of the bacterial genes via homologous recombination after transfection of BACs into cell culture. The BAC-CHV system was used to produce a recombinant virus that constitutively expressed porcine zona pellucida subunit C protein between the UL21 and UL22 genes of CHV. Complete self-excision of the bacterial genes from CHV was achieved within one round of replication whilst retaining antigen gene expression.

  8. Diverse pathogenicity of equine herpesvirus 1 (EHV-1) isolates in CBA mouse model.

    Science.gov (United States)

    Yu, Mi Htay Htay; Kasem, Samy Gomaa Ahmed; Tsujimura, Koji; Matsumura, Tomio; Yanai, Tokuma; Yamaguchi, Tsuyoshi; Ohya, Kenji; Fukushi, Hideto

    2010-03-01

    The pathogenicity of equine herpesvirus 1 (EHV-1) isolates of Japan were evaluated by using the CBA mouse model. CBA mice were inoculated with eight Japanese EHV-1 strains (89c1, 90c16, 90c18, 97c11, 98c12, 00c19, 01c1 and HH-1) and one British strain (Ab4p). 89c1 caused slight body weight loss and nervous signs in mice at 8 days post infection (dpi). Severe weight loss and nervous signs were observed in mice inoculated with Ab4p at 6 dpi. The other strains did not cause apparent clinical signs. Infectious viruses were recovered from the lungs of all groups at 2 dpi. Histopathological analysis revealed interstitial pneumonia in the lungs of all mice inoculated with EHV-1. Encephalitis or meningoencephalitis was observed in the brains of mice inoculated with 89c1, 90c18, 97c11, 98c12, 01c1 and Ab4p. Japanese EHV-1 strains showed low pathogenicity in CBA mice, whereas the sequential affects of infection are similar to those of the highly pathogenic strain Ab4p. These results suggest that field isolates of EHV-1 have varying degrees of pathogenicity in CBA mice.

  9. CLINICAL INFECTION OF CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 4.

    Science.gov (United States)

    Fuery, Angela; Browning, Geoffrey R; Tan, Jie; Long, Simon; Hayward, Gary S; Cox, Sherry K; Flanagan, Joseph P; Tocidlowski, Maryanne E; Howard, Lauren L; Ling, Paul D

    2016-03-01

    Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease in juvenile Asian elephants. A number of EEHV types and subtypes exist, where most deaths have been caused by EEHV1A and EEHV1B. EEHV4 has been attributed to two deaths, but as both diagnoses were made postmortem, EEHV4 disease has not yet been observed and recorded clinically. In this brief communication, two cases of EEHV4 infection in juvenile elephants at the Houston Zoo are described, where both cases were resolved following intensive treatment and administration of famciclovir. A quantitative real-time polymerase chain reaction detected EEHV4 viremia that correlated with clinical signs. High levels of EEHV4 shedding from trunk wash secretions of the first viremic elephant correlated with subsequent infection of the second elephant with EEHV4. It is hoped that the observations made in these cases--and the successful treatment regimen used--will help other institutions identify and treat EEHV4 infection in the future.

  10. Intracellular trafficking of VP22 in bovine herpesvirus-1 infected cells

    International Nuclear Information System (INIS)

    Lobanov, Vladislav A.; Babiuk, Lorne A.; Drunen Littel-van den Hurk, Sylvia van

    2010-01-01

    The intracellular trafficking of different VP22-enhanced yellow fluorescent protein (EYFP) fusion proteins expressed by bovine herpesvirus-1 (BHV-1) recombinants was examined by live-cell imaging. Our results demonstrate that (i) the fusion of EYFP to the C terminus of VP22 does not alter the trafficking of the protein in infected cells, (ii) VP22 expressed during BHV-1 infection translocates to the nucleus through three different pathways, namely early mitosis-dependent nuclear translocation, late massive nuclear translocation that follows a prolonged cytoplasmic stage of the protein in non-mitotic cells, and accumulation of a small subset of VP22 in discrete dot-like nuclear domains during its early cytoplasmic stage, (iii) the addition of the SV40 large-T-antigen nuclear localization signal (NLS) to VP22-EYFP abrogates its early cytoplasmic stage, and (iv) the VP22 131 PRPR 134 NLS is not required for the late massive nuclear translocation of the protein, but this motif is essential for the targeting of VP22 to discrete dot-like nuclear domains during the early cytoplasmic stage. These results show that the amount of VP22 in the nucleus is precisely regulated at different stages of BHV-1 infection and suggest that the early pathways of VP22 nuclear accumulation may be more relevant to the infection process as the late massive nuclear influx starts when most of the viral progeny has already emerged from the cell.

  11. Genetic and antigenic relatedness of bovine herpesvirus-1 and pseudorabies virus

    International Nuclear Information System (INIS)

    Bush, C.E.

    1985-01-01

    The DNA sequence homology between the genomes of bovine herpesvirus-1 (BHV-1) and pseudorabies virus (PRV) was examined. Reciprocal cross hybridization of viral DNA labeled by nick translation to Southern blots of Kpnl, BamH1, EcoR1, and HindIII restriction endonuclease digested DNA, detected homologous sequences dispersed throughout the genomes of the two viruses. The DNA-DNA hybrids were found to be stable under high stringency wash conditions. Sequences of a 32 P-labeled PRV DNA A fragment probe were found to hybridize only to the BHV-1 HindIII G fragment. This indicated that the sequence homology detected between these two viruses was not simply due to fortuitous hybridization of guanine plus cytosine rich sequences. The homology between BHV-1 and PRV was determined by liquid reassociation. It was found that the hybridization rates between 32 P-labeled PRV DNA and unlabeled BHV-1 DNA and 32 P-labeled BHV-1 DNA and unlabeled PRV DNA corresponded to approximately 8% reassociation. The antigenic relatedness between BHV-1 and PRV was also examined. Eighty percent plaque reduction serum neutralization tests showed that BHV-1 rabbit hyperimmune antiserum neutralized BHV-1 virus at a serum neutralization titer (SNT) of 1:256 and PRV virus at an (SNT) of 1:8. PRV rabbit hyperimmune antiserum neutralized PRV virus at an SNT of 1:4 and BHV-1 virus at an SNT of 1:2

  12. Detection of koi herpesvirus (KHV) using a monoclonal antibody against Cyprinus carpio IgM.

    Science.gov (United States)

    Li, Yingying; Zheng, Shucheng; Wang, Qing; Bergmann, Sven M; Zeng, Weiwei; Wang, Yingying; Liu, Chun; Shi, Cunbin

    2017-08-01

    Koi herpesvirus disease (KHVD) is associated with high mortality in both common carp and koi carp (Cyprinus carpio L.) worldwide. The indirect detection of fish viruses based on the identification of antibodies has emerged as a practical and reliable means of diagnosis. Thus, it is important to create monoclonal antibodies (MAbs) against carp IgM. By using hybridoma-monoclonal antibody technology, one hybridoma cell line secreting MAbs against IgM from carp was established. In western blot analysis, the secreted MAb from cell line A5-E10 recognized the heavy chain of IgM from common carp or koi but did not react with immunoglobulins from three different fish species: grass carp (Ctenopharyngodon idella), tilapia (Oreochromis mossambicus) and Mandarin fish (Siniperca chuatsi). These results demonstrated that this MAb is highly specific for the IgM of carp and suggested that it can be used for monitoring the immunity level of carp, for example for indirect KHV diagnosis by antibody ELISA. We therefore established an indirect ELISA, which was tested using 200 serum samples from koi from three farms. The final results showed that 147 (73.5%) samples were confirmed to be KHV antibody negative and 53 (26.5%) were definitely positive, containing antibodies against KHV.

  13. Development of a recombinant poxvirus expressing bovine herpesvirus-1 glycoprotein D

    International Nuclear Information System (INIS)

    Ruiz Saenz, Julian; Osorio, Jorge E; Vera, Victor J.

    2012-01-01

    Bovine herpesvirus-1 is a DNA virus belonging to the family herpesviridae, which affects cattle, causing a wide spectrum of clinical manifestations and economic losses. The main immunogenic component is its envelope glycoprotein d (GD), which has been characterized and used as immunogen in different expression systems. The aim of this work was to generate a recombinant poxvirus (raccoonpox [RCN]) expressing a truncated version of BHV-1 GD to be used as a vaccine. to do this, it was amplified the gene for a truncated version of GD which subsequently was cloned in transfer plasmid PTK/IRES/TPA which has homology to sites of poxvirus thymidine kinase, an internal site of ribosome entry (IRES) and a secretory signal (TPA), generating the construct PTK/GD/IRES/TPA. to generate the recombinant RCN, we took BSC-1 cells and we infected with a wild type RCN (CDC/v71-i-85a) at a multiplicity of infection of 0.05, then cells were transfected with the construct PTK/GD/IRES/TPA, generating different viral populations with and without the gene of interest. To select recombinant viruses expressing the gene of interest, we performed a selection of recombinant thymidine kinase negative and positive for GD by three rounds of plaque purification on rat-2 cells monolayers which are thymidine kinase null and using bromodeoxyuridine. Recombinant viruses were recovered and confirmed by PCR and nucleotide sequencing and so called RCN-GD.

  14. Cyprinid herpesvirus 2 infection emerged in cultured gibel carp, Carassius auratus gibelio in China.

    Science.gov (United States)

    Xu, Jin; Zeng, Lingbing; Zhang, Hui; Zhou, Yong; Ma, Jie; Fan, Yuding

    2013-09-27

    An epizootic with severe mortality has emerged in cultured gibel carp, Carassius auratus gibelio, in China since 2009, and caused huge economic loss. The signs and epidemiology background of the disease were investigated. Parasite examination, bacteria and virus isolation were carried out for pathogen isolation. The causative pathogen was obtained and identified as Cyprinid herpesvirus 2 (CyHV-2) by experimental infection, electron microscopy, cell culture, PCR assay and sequence alignment, designated as CyHV-2-JSSY. Experimental infection proved the high virulence of CyHV-2-JSSY to healthy gibel carp. Electron microscopy revealed that the viral nucleocapsid was hexagonal in shape measuring 110-120 nm in diameter with a 170-200 nm envelope. The virus caused significant CPE in Koi-Fin cells at the early passages, but not beyond the fifth passages. Sequence alignment of the partial viral helicase gene (JX566884) showed that it shared 99-100% identity to the published sequences of other CyHV-2 isolates. This study represented the first isolation and identification of CyHV-2 in cultured gibel carp in China and laid a foundation for the further studies of the disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Pathogenicity of a Very Virulent Strain of Marek's Disease Herpesvirus Cloned as Infectious Bacterial Artificial Chromosomes

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    Lorraine P. Smith

    2011-01-01

    Full Text Available Bacterial artificial chromosome (BAC vectors containing the full-length genomes of several herpesviruses have been used widely as tools to enable functional studies of viral genes. Marek's disease viruses (MDVs are highly oncogenic alphaherpesviruses that induce rapid-onset T-cell lymphomas in chickens. Oncogenic strains of MDV reconstituted from BAC clones have been used to examine the role of viral genes in inducing tumours. Past studies have demonstrated continuous increase in virulence of MDV strains. We have previously reported on the UK isolate C12/130 that showed increased virulence features including lymphoid organ atrophy and enhanced tropism for the central nervous system. Here we report the construction of the BAC clones (pC12/130 of this strain. Chickens were infected with viruses reconstituted from the pC12/130 clones along with the wild-type virus for the comparison of the pathogenic properties. Our studies show that BAC-derived viruses induced disease similar to the wild-type virus, though there were differences in the levels of pathogenicity between individual viruses. Generation of BAC clones that differ in the potential to induce cytolytic disease provide the opportunity to identify the molecular determinants of increased virulence by direct sequence analysis as well as by using reverse genetics approaches on the infectious BAC clones.

  16. Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti.

    Science.gov (United States)

    Marcelin, Anne-Geneviève; Grandadam, Marc; Flandre, Philippe; Nicand, Elisabeth; Milliancourt, Catherine; Koeck, Jean-Louis; Philippon, Michel; Teyssou, Remy; Agut, Henri; Dupin, Nicolas; Calvez, Vincent

    2002-10-01

    Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma. Epidemiological studies have shown that KSHV transmission can occur during sex among homosexual men, but heterosexual transmission seems to be very rare in KSHV low prevalence countries. A seroepidemiological study was conducted to determine whether KSHV is transmitted sexually between heterosexuals in an endemic country. Sera from 282 subjects of African origin living in Djibouti were tested for antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female prostitutes working in the streets (group 1), 123 were female prostitutes working in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34 and OR = 1.18; P = 0.73). These results suggest that in this endemic country commercial sex work does not seem to be a risk factor for KSHV infection and provides evidence against heterosexual transmission of KSHV in the female population studied. Copyright 2002 Wiley-Liss, Inc.

  17. Four levels of hierarchical organization, including noncovalent chainmail, brace the mature tumor herpesvirus capsid against pressurization.

    Science.gov (United States)

    Zhou, Z Hong; Hui, Wong Hoi; Shah, Sanket; Jih, Jonathan; O'Connor, Christine M; Sherman, Michael B; Kedes, Dean H; Schein, Stan

    2014-10-07

    Like many double-stranded DNA viruses, tumor gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus withstand high internal pressure. Bacteriophage HK97 uses covalent chainmail for this purpose, but how this is achieved noncovalently in the much larger gammaherpesvirus capsid is unknown. Our cryoelectron microscopy structure of a gammaherpesvirus capsid reveals a hierarchy of four levels of organization: (1) Within a hexon capsomer, each monomer of the major capsid protein (MCP), 1,378 amino acids and six domains, interacts with its neighboring MCPs at four sites. (2) Neighboring capsomers are linked in pairs by MCP dimerization domains and in groups of three by heterotrimeric triplex proteins. (3) Small (∼280 amino acids) HK97-like domains in MCP monomers alternate with triplex heterotrimers to form a belt that encircles each capsomer. (4) One hundred sixty-two belts concatenate to form noncovalent chainmail. The triplex heterotrimer orchestrates all four levels and likely drives maturation to an angular capsid that can withstand pressurization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Seroprevalence of Kaposi's sarcoma-associated herpesvirus in various populations in Cuba Seroprevalencia del herpesvirus asociado con el sarcoma de Kaposi en diversas poblaciones en Cuba

    Directory of Open Access Journals (Sweden)

    Vivian Kourí

    2004-05-01

    Full Text Available OBJECTIVE: Little is known about the prevalence and distribution of Kaposi's sarcoma-associated herpesvirus (KSHV infection in the Caribbean. The aim of this study was to determine rates of KSHV seropositivity in various populations in Cuba. METHODS: During the years 1998 to 2002 we screened serum samples from 410 subjects in Cuba. Serologic screening for KSHV antibodies was a two-step process using (1 indirect immunofluorescence assay (IFA specifically reactive to the KSHV latency-associated nuclear antigen (LANA encoded by open reading frame 73 (ORF73, and (2 confirmatory immunoblot using recombinant KSHV ORF65.2, a lytically expressed, 20-kilodalton protein as the target antigen. Five different populations were studied: (1 45 AIDS patients with Kaposi's sarcoma (AIDS-KS, (2 154 HIV-1-infected patients without clinical evidence of KS, (3 171 HIV-negative blood donors, (4 27 consecutive kidney transplant recipients, who were HIV-negative, and (5 13 contacts (sexual contacts or relatives of the AIDS-KS-affected patients. RESULTS: Among the 45 AIDS-KS subjects, 35 of them (77.8% were KSHV-seropositive. Thirty-two of the 154 HIV-positive patients without KS (20.8% of them were KSHV-seropositive, and 6 of the 13 contacts of KS-affected patients (46.2% of them were infected with KSHV. In contrast to other researchers, we did not find in the populations that we studied in Cuba that KSHV seropositivity was associated with male homosexual or bisexual activity. We found high KSHV seropositivity rates among women reporting sexual contact with bisexual men and among men who had acquired an HIV infection in Africa. There were low rates of KSHV infection among the blood donors (1.2% and the renal transplant recipients (0.0%. The low rates of KSHV infection that we found among the non-HIV-infected populations in Cuba are similar to patterns found in populations in Europe and in the United States. CONCLUSIONS: Together with similar results from Brazil

  19. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection

    Directory of Open Access Journals (Sweden)

    Benjamin A. Diner

    2016-11-01

    Full Text Available The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS. Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1 and human cytomegalovirus (HCMV infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses.

  20. The Genome of a Tortoise Herpesvirus (Testudinid Herpesvirus 3) Has a Novel Structure and Contains a Large Region That Is Not Required for Replication In Vitro or Virulence In Vivo

    Science.gov (United States)

    Gandar, Frédéric; Wilkie, Gavin S.; Gatherer, Derek; Kerr, Karen; Marlier, Didier; Diez, Marianne; Marschang, Rachel E.; Mast, Jan; Dewals, Benjamin G.

    2015-01-01

    ABSTRACT Testudinid herpesvirus 3 (TeHV-3) is the causative agent of a lethal disease affecting several tortoise species. The threat that this virus poses to endangered animals is focusing efforts on characterizing its properties, in order to enable the development of prophylactic methods. We have sequenced the genomes of the two most studied TeHV-3 strains (1976 and 4295). TeHV-3 strain 1976 has a novel genome structure and is most closely related to a turtle herpesvirus, thus supporting its classification into genus Scutavirus, subfamily Alphaherpesvirinae, family Herpesviridae. The sequence of strain 1976 also revealed viral counterparts of cellular interleukin-10 and semaphorin, which have not been described previously in members of subfamily Alphaherpesvirinae. TeHV-3 strain 4295 is a mixture of three forms (m1, m2, and M), in which, in comparison to strain 1976, the genomes exhibit large, partially overlapping deletions of 12.5 to 22.4 kb. Viral subclones representing these forms were isolated by limiting dilution assays, and each replicated in cell culture comparably to strain 1976. With the goal of testing the potential of the three forms as attenuated vaccine candidates, strain 4295 was inoculated intranasally into Hermann's tortoises (Testudo hermanni). All inoculated subjects died, and PCR analyses demonstrated the ability of the m2 and M forms to spread and invade the brain. In contrast, the m1 form was detected in none of the organs tested, suggesting its potential as the basis of an attenuated vaccine candidate. Our findings represent a major step toward characterizing TeHV-3 and developing prophylactic methods against it. IMPORTANCE Testudinid herpesvirus 3 (TeHV-3) causes a lethal disease in tortoises, several species of which are endangered. We have characterized the viral genome and used this information to take steps toward developing an attenuated vaccine. We have sequenced the genomes of two strains (1976 and 4295), compared their growth in

  1. Counting the dead to determine the source and transmission of the marine herpesvirus OsHV-1 in Crassostrea gigas.

    Science.gov (United States)

    Whittington, Richard J; Paul-Pont, Ika; Evans, Olivia; Hick, Paul; Dhand, Navneet K

    2018-04-10

    Marine herpesviruses are responsible for epizootics in economically, ecologically and culturally significant taxa. The recent emergence of microvariants of Ostreid herpesvirus 1 (OsHV-1) in Pacific oysters Crassostrea gigas has resulted in socioeconomic losses in Europe, New Zealand and Australia however, there is no information on their origin or mode of transmission. These factors need to be understood because they influence the way the disease may be prevented and controlled. Mortality data obtained from experimental populations of C. gigas during natural epizootics of OsHV-1 disease in Australia were analysed qualitatively. In addition we compared actual mortality data with those from a Reed-Frost model of direct transmission and analysed incubation periods using Sartwell's method to test for the type of epizootic, point source or propagating. We concluded that outbreaks were initiated from an unknown environmental source which is unlikely to be farmed oysters in the same estuary. While direct oyster-to-oyster transmission may occur in larger oysters if they are in close proximity (< 40 cm), it did not explain the observed epizootics, point source exposure and indirect transmission being more common and important. A conceptual model is proposed for OsHV-1 index case source and transmission, leading to endemicity with recurrent seasonal outbreaks. The findings suggest that prevention and control of OsHV-1 in C. gigas will require multiple interventions. OsHV-1 in C. gigas, which is a sedentary animal once beyond the larval stage, is an informative model when considering marine host-herpesvirus relationships.

  2. Bovine herpesvirus type-1 glycoprotein K (gK) interacts with UL20 and is required for infectious virus production

    Energy Technology Data Exchange (ETDEWEB)

    Haque, Muzammel; Stanfield, Brent; Kousoulas, Konstantin G.

    2016-12-15

    We have previously shown that the HSV-1 gK and UL20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. Alignment of the predicted secondary structures of gKs encoded by BoHV-1, HSV-1, HSV-2, EHV-1 and VZV indicated a high degree of domain conservation. Two BoHV-1 gK-null mutant viruses were created by either gK gene deletion or stop codon insertion. In addition, a V5 epitope-tag was inserted at the carboxyl terminus of gK gene to detect gK. The engineered gK-null mutant viruses failed to replicate and produce viral plaques. Co-immunoprecipitation of gK and UL20 expressed via different methods revealed that gK and UL20 physically interacted in the presence or absence of other viral proteins. Confocal microscopy showed that gK and UL20 colocalized in infected cells. These results indicate that BoHV-1 gK and UL20 may function in a similar manner to other alphaherpesvirus orthologues specified by HSV-1, PRV and EHV-1. -- Highlights: •Glycoprotein K(gK) is conserved among alphaherpesviruses and serves similar functions. •The bovine herpesvirus-1 gK and UL20 proteins physically interact in a similar manner to herpes simplex virus type 1 and equine herpesvirus-1. •The bovine herpesvirus-1 (BoHV-1) gK interacts with UL20 and is essential for virus replication and spread.

  3. Bovine herpesvirus type-1 glycoprotein K (gK) interacts with UL20 and is required for infectious virus production

    International Nuclear Information System (INIS)

    Haque, Muzammel; Stanfield, Brent; Kousoulas, Konstantin G.

    2016-01-01

    We have previously shown that the HSV-1 gK and UL20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. Alignment of the predicted secondary structures of gKs encoded by BoHV-1, HSV-1, HSV-2, EHV-1 and VZV indicated a high degree of domain conservation. Two BoHV-1 gK-null mutant viruses were created by either gK gene deletion or stop codon insertion. In addition, a V5 epitope-tag was inserted at the carboxyl terminus of gK gene to detect gK. The engineered gK-null mutant viruses failed to replicate and produce viral plaques. Co-immunoprecipitation of gK and UL20 expressed via different methods revealed that gK and UL20 physically interacted in the presence or absence of other viral proteins. Confocal microscopy showed that gK and UL20 colocalized in infected cells. These results indicate that BoHV-1 gK and UL20 may function in a similar manner to other alphaherpesvirus orthologues specified by HSV-1, PRV and EHV-1. -- Highlights: •Glycoprotein K(gK) is conserved among alphaherpesviruses and serves similar functions. •The bovine herpesvirus-1 gK and UL20 proteins physically interact in a similar manner to herpes simplex virus type 1 and equine herpesvirus-1. •The bovine herpesvirus-1 (BoHV-1) gK interacts with UL20 and is essential for virus replication and spread.

  4. A Quantitative Polymerase Chain Reaction Assay for the Detection and Quantification of Epizootic Epitheliotropic Disease Virus (EEDV; Salmonid Herpesvirus 3).

    Science.gov (United States)

    Glenney, Gavin W; Barbash, Patricia A; Coll, John A

    2016-03-01

    Epizootic epitheliotropic disease virus (EEDV; salmonid herpesvirus [SalHV3]; family Alloherpesviridae) causes a systemic disease of juvenile and yearling Lake Trout Salvelinus namaycush. No cell lines are currently available for the culture and propagation of EEDV, so primary diagnosis is limited to PCR and electron microscopy. To better understand the pervasiveness of EEDV (carrier or latent state of infection) in domesticated and wild Lake Trout populations, we developed a sensitive TaqMan quantitative PCR (qPCR) assay to detect the presence of the EEDV terminase gene in Lake Trout tissues. This assay was able to detect a linear standard curve over nine logs of plasmid dilution and was sensitive enough to detect single-digit copies of EEDV. The efficiency of the PCR assay was 99.4 ± 0.06% (mean ± SD), with a 95% confidence limit of 0.0296 (R(2) = 0.994). Methods were successfully applied to collect preliminary data from a number of species and water bodies in the states of Pennsylvania, New York, and Vermont, indicating that EEDV is more common in wild fish than previously known. In addition, through the development of this qPCR assay, we detected EEDV in a new salmonid species, the Cisco Coregonus artedi. The qPCR assay was unexpectedly able to detect two additional herpesviruses, the Atlantic Salmon papillomatosis virus (ASPV; SalHV4) and the Namaycush herpesvirus (NamHV; SalHV5), which both share high sequence identity with the EEDV terminase gene. With these unexpected findings, we subsequently designed three primer sets to confirm initial TaqMan qPCR assay positives and to differentiate among EEDV, ASPV, and NamHV by detecting the glycoprotein genes via SYBR Green qPCR. Received April 20, 2015; accepted November 10, 2015.

  5. The seroprevalence and salivary shedding of herpesviruses in Behçet's syndrome and recurrent aphthous stomatitis

    Directory of Open Access Journals (Sweden)

    Noha Seoudi

    2015-06-01

    Full Text Available Background: Behçet's syndrome (BS is one of the multisystemic diseases that presents with oral ulceration and several other systemic manifestations including genital ulceration, folliculitis, erythema nodosum-like lesions, uveitis, and arthropathy. Ocular manifestation, central nervous system involvement, and gastrointestinal manifestation account for most of the complications of this disease, whereas orogenital ulceration and dermatological involvement affects the quality of life. The cause of the disease is not fully elucidated; however, herpesviruses have long been thought to play a pivotal role in the disease pathogenesis. Objective: To investigate the seroprevalence and salivary shedding of herpesviruses in BS. Method: The levels of specific immunoglobulin G in six different herpesviruses in serum samples collected from 54 BS, 28 healthy controls (HC, and 7 recurrent aphthous stomatitis (RAS patients were investigated. Salivary viral load was also quantified for these viruses in matched saliva samples using quantitative real-time polymerase chain reaction. Results: The BS had lower cytomegalovirus (CMV IgG level in comparison to HC (p=0.0226 and RAS (p=0.0450. There was statistically significant higher salivary shedding of Epstein-Barr virus (EBV in BS in comparison to HC (p=0.0052, but not RAS (p=0.3318. Conclusions: A high EBV shedding was observed in both BS and RAS and a lower level of CMV IgG was observed in BS only. The reason for the observed lower level of CMV IgG in BS is not clear. However, one explanation might be a defect in the cross-talk between innate and adaptive immune responses which was suggested by a previously described defect in the toll-like receptor 1 and 2 heterodimer formation and function, this being the initial receptor sensing of CMV.

  6. RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.

    Science.gov (United States)

    Sim, Richard R; Allender, Matthew C; Crawford, LaTasha K; Wack, Allison N; Murphy, Kevin J; Mankowski, Joseph L; Bronson, Ellen

    2016-03-01

    Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases. The remaining 22 animals were isolated, segregated by severity of clinical signs, and treated with nutritional support, fluid therapy, ambient temperature management, antibiotics, and antiviral therapy. Oral swabs were tested serially for FV3-like virus by quantitative real-time PCR (qPCR) and tested at day 0 for herpesvirus and Mycoplasma sp. by conventional PCR. With oral swabs, 77% of the 22 turtles were FV3-like virus positive; however, qPCR on tissues taken during necropsy revealed the true prevalence was 86%. FV3-like virus prevalence and the median number of viral copies being shed significantly declined during the outbreak. The prevalence of herpesvirus and Mycoplasma sp. by PCR of oral swabs at day 0 was 55% and 68%, respectively. The 58% survival rate was higher than previously reported in captive eastern box turtles for a ranavirus epizootic. All surviving turtles brumated normally and emerged the following year with no clinical signs during subsequent monitoring. The immediate initiation of treatment and intensive supportive care were considered the most important contributing factors to the successful outcome in this outbreak.

  7. DNA-polymerase induced by Herpesvirus papio (HVP) in cells of lymphoblastoid cultures derived from lymphomatous baboons. Report V.

    Science.gov (United States)

    Djachenko, A G; Lapin, B A

    1981-01-01

    A new DNA-polymerase was found in the cells of suspension lymphoblastoid cultures which produce lymphotropic baboon herpesvirus (HVP). This enzyme was isolated in a partially purified form. Some of its properties vary from those of other cellular DNA-polymerases. HVP-induced DNA-polymerase has a molecule weight of 160,000 and sedimentation coefficient of about 8 S. The enzyme is resistant to high salt concentration and N-ethylmaleimide, but it is very sensitive to phosphonoacetate. It effectively copies "activated" DNA and synthetic deoxyribohomopolymers. Attempts to reveal the DNA-polymerase activity in HVP virions were unsuccessful.

  8. Immunization of dogs with a canine herpesvirus vector expressing Neospora caninum surface protein, NcSRS2.

    Science.gov (United States)

    Nishikawa, Y; Ikeda, H; Fukumoto, S; Xuan, X; Nagasawa, H; Otsuka, H; Mikami, T

    2000-10-01

    In order to develop a vaccine against Neospora caninum in dogs, we constructed recombinant canine herpesvirus (CHV) expressing N. caninum surface protein, NcSRS2. Indirect immunofluorescence indicated that the antigenic structure of the recombinant NcSRS2 was similar to the authentic parasite protein. The dogs immunised with recombinant virus produced IgG antibody to N. caninum, and their sera recognised the parasite protein on Western blot. The dogs inoculated with recombinant virus showed no clinical symptoms and infectious CHV was not recovered from the dogs, suggesting that recombinant CHV expressing N. caninum proteins may lead to a vaccine against neosporosis in dogs.

  9. Australian abalone (Haliotis laevigata, H. rubra and H. conicopora) are susceptible to infection by multiple abalone herpesvirus genotypes.

    Science.gov (United States)

    Corbeil, Serge; Williams, Lynette M; McColl, Kenneth A; Crane, Mark St J

    2016-05-03

    From 2006 to 2012, acute mortalities occurred in farmed and wild abalone (Haliotis spp.) along the coast of Victoria, Australia. The disease (abalone viral ganglioneuritis; AVG) is associated with infection by an abalone herpesvirus (AbHV). The relative pathogenicity of 5 known variants of AbHV was evaluated on abalone stocks from different states in Australia. Results indicated that all virus variants (Vic1, Tas1, Tas2, Tas3 and Tas4) cause disease and mortality in all abalone stocks tested (greenlip, blacklip and brownlip). In order to avoid further AVG outbreaks in Australian wild abalone, strict regulations on the transfer of abalone stocks must be implemented.

  10. The viral G protein-coupled receptor ORF74 hijacks β-arrestins for endocytic trafficking in response to human chemokines

    NARCIS (Netherlands)

    De Munnik, Sabrina M.; Kooistra, Albert J.; Van Offenbeek, Jody; Nijmeijer, Saskia; de Graaf, C.; Smit, Martine J.; Leurs, Rob; Vischer, Henry F.

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus-infected cells express the virally encoded G protein-coupled receptor ORF74. Although ORF74 is constitutively active, it binds human CXC chemokines that modulate this basal activity. ORF74-induced signaling has been demonstrated to underlie the development of

  11. m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveal