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Sample records for herpesvirus lytic switch

  1. Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

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    Aneja, Kawalpreet K.; Yuan, Yan

    2017-01-01

    The life cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of two phases, latent and lytic. The virus establishes latency as a strategy for avoiding host immune surveillance and fusing symbiotically with the host for lifetime persistent infection. However, latency can be disrupted and KSHV is reactivated for entry into the lytic replication. Viral lytic replication is crucial for efficient dissemination from its long-term reservoir to the sites of disease and for the spread of the virus to new hosts. The balance of these two phases in the KSHV life cycle is important for both the virus and the host and control of the switch between these two phases is extremely complex. Various environmental factors such as oxidative stress, hypoxia, and certain chemicals have been shown to switch KSHV from latency to lytic reactivation. Immunosuppression, unbalanced inflammatory cytokines, and other viral co-infections also lead to the reactivation of KSHV. This review article summarizes the current understanding of the initiation and regulation of KSHV reactivation and the mechanisms underlying the process of viral lytic replication. In particular, the central role of an immediate-early gene product RTA in KSHV reactivation has been extensively investigated. These studies revealed multiple layers of regulation in activation of RTA as well as the multifunctional roles of RTA in the lytic replication cascade. Epigenetic regulation is known as a critical layer of control for the switch of KSHV between latency and lytic replication. The viral non-coding RNA, PAN, was demonstrated to play a central role in the epigenetic regulation by serving as a guide RNA that brought chromatin remodeling enzymes to the promoters of RTA and other lytic genes. In addition, a novel dimension of regulation by microPeptides emerged and has been shown to regulate RTA expression at the protein level. Overall, extensive investigation of KSHV reactivation and lytic replication has revealed

  2. Epstein-Barr virus (EBV Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

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    Yen-Ju Chen

    Full Text Available Epstein-Barr virus (EBV Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1 an ideal environment for virus reactivation if EBV or KSHV coexists and (2 a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  3. 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

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

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    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

  5. Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication

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    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...

  6. 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.

  7. Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

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    Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

    2014-01-01

    ABSTRACT The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCE Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota

  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.

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    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. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome.

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    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

  10. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

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    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

  11. Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.

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    He, Zhiheng; Liu, Yunhua; Liang, Deguang; Wang, Zhuo; Robertson, Erle S; Lan, Ke

    2010-02-01

    Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.

  12. The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens.

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    Rebecca C Robey

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is causally related to Kaposi's sarcoma (KS, the most common malignancy in untreated individuals with HIV/AIDS. The adaptive T-cell immune response against KSHV has not been fully characterized. To achieve a better understanding of the antigenic repertoire of the CD8 and CD4 T-cell responses against KSHV, we constructed a library of lentiviral expression vectors each coding for one of 31 individual KSHV open reading frames (ORFs. We used these to transduce monocyte-derived dendritic cells (moDCs isolated from 14 KSHV-seropositive (12 HIV-positive and 7 KSHV-seronegative (4 HIV-positive individuals. moDCs were transduced with up to 3 KSHV ORFs simultaneously (ORFs grouped according to their expression during the viral life cycle. Transduced moDCs naturally process the KSHV genes and present the resulting antigens in the context of MHC class I and II. Transduced moDCs were cultured with purified autologous T cells and the CD8 and CD4 T-cell proliferative responses to each KSHV ORF (or group was assessed using a CFSE dye-based assay. Two pools of early lytic KSHV genes ([ORF8/ORF49/ORF61] and [ORF59/ORF65/K4.1] were frequently-recognized targets of both CD8 and CD4 T cells from KSHV seropositive individuals. One pool of late lytic KSHV genes ([ORF28/ORF36/ORF37] was a frequently-recognized CD8 target and another pool of late genes ([ORF33/K1/K8.1] was a frequently-recognized CD4 target. We report that both the CD8 and CD4 T-cell responses against KSHV are skewed towards genes expressed in the early and late phases of the viral lytic cycle, and identify some previously unknown targets of these responses. This knowledge will be important to future immunological investigations into KSHV and may eventually lead to the development of better immunotherapies for KSHV-related diseases.

  13. The lytic origin of herpesvirus papio is highly homologous to Epstein-Barr virus ori-Lyt: evolutionary conservation of transcriptional activation and replication signals.

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    Ryon, J J; Fixman, E D; Houchens, C; Zong, J; Lieberman, P M; Chang, Y N; Hayward, G S; Hayward, S D

    1993-01-01

    Herpesvirus papio (HVP) is a B-lymphotropic baboon virus with an estimated 40% homology to Epstein-Barr virus (EBV). We have cloned and sequenced ori-Lyt of herpesvirus papio and found a striking degree of nucleotide homology (89%) with ori-Lyt of EBV. Transcriptional elements form an integral part of EBV ori-Lyt. The promoter and enhancer domains of EBV ori-Lyt are conserved in herpesvirus papio. The EBV ori-Lyt promoter contains four binding sites for the EBV lytic cycle transactivator Zta, and the enhancer includes one Zta and two Rta response elements. All five of the Zta response elements and one of the Rta motifs are conserved in HVP ori-Lyt, and the HVP DS-L leftward promoter and the enhancer were activated in transient transfection assays by the EBV Zta and Rta transactivators. The EBV ori-Lyt enhancer contains a palindromic sequence, GGTCAGCTGACC, centered on a PvuII restriction site. This sequence, with a single base change, is also present in the HVP ori-Lyt enhancer. DNase I footprinting demonstrated that the PvuII sequence was bound by a protein present in a Raji nuclear extract. Mobility shift and competition assays using oligonucleotide probes identified this sequence as a binding site for the cellular transcription factor MLTF. Mutagenesis of the binding site indicated that MLTF contributes significantly to the constitutive activity of the ori-Lyt enhancer. The high degree of conservation of cis-acting signal sequences in HVP ori-Lyt was further emphasized by the finding that an HVP ori-Lyt-containing plasmid was replicated in Vero cells by a set of cotransfected EBV replication genes. The central domain of EBV ori-Lyt contains two related AT-rich palindromes, one of which is partially duplicated in the HVP sequence. The AT-rich palindromes are functionally important cis-acting motifs. Deletion of these palindromes severely diminished replication of an ori-Lyt target plasmid. Images PMID:8389916

  14. 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)

  15. Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of Kaposi's sarcoma-associated herpesvirus

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    Staudt, Michelle R.; Dittmer, Dirk P.

    2006-01-01

    Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity

  16. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

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    Lv Zhigang

    2011-10-01

    Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS, primary effusion lymphoma (PEL and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1 was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV. Results By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1/signal transducer and activator of transcription 3 (STAT3 or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K/protein kinase B (PKB, also called AKT pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN and glycogen synthase kinase-3β (GSK-3β. PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK mitogen-activated protein kinase (MAPK pathway also partially contributed to HSV-1-induced KSHV replication. Conclusions HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.

  17. Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

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    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.

  18. Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation.

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    Huang, Lu; Yang, Mengtian; Yuan, Yan; Li, Xiaojuan; Kuang, Ersheng

    2017-02-01

    Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication. Consequently, niclosamide effectively suppresses EBV lytic gene expression, viral DNA lytic replication and virion production in EBV-infected lymphoma cells and epithelial cells. Niclosamide exhibits cytotoxicity toward lymphoma cells and induces irreversible cell cycle arrest in lytically EBV-infected cells. The ectopic overexpression of mTOR reverses the inhibition of niclosamide in EBV lytic replication. Similarly, niclosamide inhibits KSHV lytic replication. Thus, we conclude that niclosamide is a promising candidate for chemotherapy against the acute occurrence and transmission of infectious diseases of oncogenic γ-herpesviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency

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    Lan, Ke; Murakami, Masanao; Choudhuri, Tathagata; Kuppers, Daniel A.; Robertson, Erle S.

    2006-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a predominantly latent infection in the infected host. Importantly, during latency, only a small number of viral encoded genes are expressed. This viral gene expression pattern contributes to the establishment of long-term infection as well as the ability of the virus to evade the immune system. Previous studies have been shown that the replication and transcription activator (RTA) encoded by ORF50 activates it downstream genes and initiates viral lytic reactivation through functional interaction with RBP-Jκ, the major downstream effector of the Notch signaling pathway. This indicates that RTA can usurp the conserved Notch signaling pathway and mimic the activities of intracellular Notch1 to modulate gene expression. In this report, we show that the activated intracellular domain of Notch1 (ICN) is aberrantly accumulated in KSHV latently infected pleural effusion lymphoma (PEL) cells. ICN activated the RTA promoter in a dose-dependent manner, and forced expression of ICN in latently infected KSHV-positive cells initiated full blown lytic replication with the production of infectious viral progeny. However, latency-associated nuclear antigen (LANA) which is predominantly expressed during latency can specifically down-modulate ICN-mediated transactivation of RTA and so control KSHV for lytic reactivation. These results demonstrate that LANA can inhibit viral lytic replication by antagonizing ICN function and suggest that LANA is a critical component of the regulatory control mechanism for switching between viral latent and lytic replication by directly interacting with effectors of the conserved cellular Notch1 pathway

  20. 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.

  1. Identification and characterization of Kaposi's sarcoma-associated herpesvirus open reading frame 11 promotor activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lei [Los Alamos National Laboratory

    2008-01-01

    Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.

  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. 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.

  4. 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.

  5. Coordination of KSHV Latent and Lytic Gene Control by CTCF-Cohesin Mediated Chromosome Conformation

    Science.gov (United States)

    Kang, Hyojeung; Wiedmer, Andreas; Yuan, Yan; Robertson, Erle; Lieberman, Paul M.

    2011-01-01

    Herpesvirus persistence requires a dynamic balance between latent and lytic cycle gene expression, but how this balance is maintained remains enigmatic. We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins. Using viral genome-wide chromatin conformation capture (3C) methods, we now show that KSHV latency control region is physically linked to the promoter regulatory region for ORF50, which encodes the KSHV immediate early protein RTA. Other linkages were also observed, including an interaction between the 5′ and 3′ end of the latency transcription cluster. Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control. siRNA depletion of CTCF or cohesin subunits also disrupted chromosomal linkages and deregulated viral latent and lytic gene transcription. Furthermore, the linkage between the latent and lytic control region was subject to cell cycle fluctuation and disrupted during lytic cycle reactivation, suggesting that these interactions are dynamic and regulatory. Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control. PMID:21876668

  6. 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.

  7. 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).

  8. 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

  9. Phage lytic enzymes: a history.

    Science.gov (United States)

    Trudil, David

    2015-02-01

    There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of 'bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

  10. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Dhananjay M Nawandar

    2015-10-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL in immunosuppressed patients. However, the cellular mechanism(s that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1 promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells.

  11. [Potentialization of antibiotics by lytic enzymes].

    Science.gov (United States)

    Brisou, J; Babin, P; Babin, R

    1975-01-01

    Few lytic enzymes, specially papaine and lysozyme, acting on the membrane and cell wall structures facilitate effects of bacitracine, streptomycine and other antibiotics. Streptomycino resistant strains became sensibles to this antibiotic after contact with papaine and lysozyme. The results of tests in physiological suspensions concern only the lytic activity of enzymes. The results on nutrient medium concern together lytic, and antibiotic activities.

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

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    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. 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.

  14. 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.

  15. 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.

  16. A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells

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    Ina Ersing

    2017-05-01

    Full Text Available Epstein-Barr virus (EBV replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.

  17. 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

  18. 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

  19. 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...

  20. 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

  1. The Murid Herpesvirus-4 gL regulates an entry-associated conformation change in gH.

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    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.

  2. 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

  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. Endoplasmic reticulum stress causes EBV lytic replication.

    Science.gov (United States)

    Taylor, Gwen Marie; Raghuwanshi, Sandeep K; Rowe, David T; Wadowsky, Robert M; Rosendorff, Adam

    2011-11-17

    Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)-specific phosphatase inhibitor Salubrinal (SAL) synergized with TG to induce EBV lytic genes; however, TG treatment alone was sufficient to activate EBV lytic replication. SAL showed ER-stress-dependent and -independent antiviral effects, preventing virus release in human LCLs and abrogating gp350 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B95-8 cells. TG resulted in sustained BCL6 but not BLIMP1 or CD138 expression, which is consistent with maintenance of a germinal center B-cell, rather than plasma-cell, phenotype. Microarray analysis identified candidate genes governing lytic replication in LCLs undergoing ER stress.

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

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    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

  6. Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

    Science.gov (United States)

    Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

    2016-02-01

    Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. © 2015 Wiley Periodicals, Inc.

  7. 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.

  8. 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.

  9. Multiple sclerosis and herpesvirus interaction

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    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.

  10. Isolation of lytic bacteriophage against Vibrio harveyi.

    Science.gov (United States)

    Crothers-Stomps, C; Høj, L; Bourne, D G; Hall, M R; Owens, L

    2010-05-01

    The isolation of lytic bacteriophage of Vibrio harveyi with potential for phage therapy of bacterial pathogens of phyllosoma larvae from the tropical rock lobster Panulirus ornatus. Water samples from discharge channels and grow-out ponds of a prawn farm in northeastern Australia were enriched for 24 h in a broth containing four V. harveyi strains. The bacteriophage-enriched filtrates were spotted onto bacterial lawns demonstrating that the bacteriophage host range for the samples included strains of V. harveyi, Vibrio campbellii, Vibrio rotiferianus, Vibrio parahaemolyticus and Vibrio proteolyticus. Bacteriophage were isolated from eight enriched samples through triple plaque purification. The host range of purified phage included V. harveyi, V. campbellii, V. rotiferianus and V. parahaemolyticus. Transmission electron microscope examination revealed that six purified phage belonged to the family Siphoviridae, whilst two belonged to the family Myoviridae. The Myoviridae appeared to induce bacteriocin production in a limited number of host bacterial strains, suggesting that they were lysogenic rather than lytic. A purified Siphoviridae phage could delay the entry of a broth culture of V. harveyi strain 12 into exponential growth, but could not prevent the overall growth of the bacterial strain. Bacteriophage with lytic activity against V. harveyi were isolated from prawn farm samples. Purified phage of the family Siphoviridae had a clear lytic ability and no apparent transducing properties, indicating they are appropriate for phage therapy. Phage resistance is potentially a major constraint to the use of phage therapy in aquaculture as bacteria are not completely eliminated. Phage therapy is emerging as a potential antibacterial agent that can be used to control pathogenic bacteria in aquaculture systems. The development of phage therapy for aquaculture requires initial isolation and determination of the bacteriophage host range, with subsequent creation of

  11. Endoplasmic reticulum stress causes EBV lytic replication

    OpenAIRE

    Taylor, Gwen Marie; Raghuwanshi, Sandeep K.; Rowe, David T.; Wadowsky, Robert M.; Rosendorff, Adam

    2011-01-01

    Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)...

  12. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication.

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    Denis Avey

    2015-07-01

    Full Text Available Kaposi's Sarcoma-Associated Herpesvirus (KSHV is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK mitogen-activated protein kinase (MAPK pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass-spectrometry-based phosphoproteomic screening identified putative substrates of ORF45-activated RSK in KSHV-infected cells. Bioinformatic analyses revealed that nuclear proteins, including several transcriptional regulators, were overrepresented among these candidates. We validated the ORF45/RSK-dependent phosphorylation of several putative substrates by employing KSHV BAC mutagenesis, kinase inhibitor treatments, and/or CRISPR-mediated knockout of RSK in KSHV-infected cells. Furthermore, we assessed the consequences of knocking out these substrates on ORF45/RSK-dependent regulation of gene expression and KSHV progeny virion production. Finally, we show data to support that ORF45 regulates the translational efficiency of a subset of viral/cellular genes with complex secondary structure in their 5' UTR. Altogether, these data shed light on the mechanisms by which KSHV ORF45

  13. 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

  14. Abortive lytic Epstein–Barr virus replication in tonsil-B lymphocytes in infectious mononucleosis and a subset of the chronic fatigue syndrome

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    Lerner AM

    2012-11-01

    Full Text Available A Martin Lerner,1 Safedin Beqaj21Department of Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA; 2Pathology Inc, Torrance, CA, USAAbstract: A systematic 2001–2007 review of 142 chronic fatigue syndrome (CFS patients identified 106 CFS patients with elevated serum IgG antibodies to the herpesviruses Epstein–Barr virus (EBV, cytomegalovirus, or human herpesvirus (HHV 6 in single or multiple infections, with no other co-infections detected. We named these 106 patients group-A CFS. Eighty-six of these 106 group-A CFS patients (81% had elevated EBV early antibody, early antigen (diffuse, serum titers. A small group of six patients in the group-A EBV subset of CFS, additionally, had repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase. The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients. None of 20 random control people (age- and sex-matched, with blood drawn at a commercial laboratory had elevated serum titers of antibody to EBV dUTPase or EBV DNA polymerase (P < 0.01. This finding needs verification in a larger group of EBV CFS subset patients, but if corroborated, it may represent a molecular marker for diagnosing the EBV subset of CFS. We review evidence that EBV abortive lytic replication with unassembled viral proteins in the blood may be the same in infectious mononucleosis (IM and a subset of CFS. EBV-abortive lytic replication in tonsil plasma cells is dominant in IM. No complete lytic virion is in the blood of IM or CFS patients. Complications of CFS and IM include cardiomyopathy and encephalopathy. Circulating abortive lytic-encoded EBV proteins (eg, EBV dUTPase, EBV DNA polymerase, and others may be common to IM and CFS. The intensity and duration of the circulating EBV-encoded proteins might differentiate the IM and EBV subsets of CFS

  15. 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

  16. Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS.

    Science.gov (United States)

    Zhang, Guigen; Chan, Baca; Samarina, Naira; Abere, Bizunesh; Weidner-Glunde, Magdalena; Buch, Anna; Pich, Andreas; Brinkmann, Melanie M; Schulz, Thomas F

    2016-02-23

    The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.

  17. Effect of supercoiling on the λ switch

    DEFF Research Database (Denmark)

    Norregaard, Kamilla; Andersson, Magnus; Sneppen, Kim

    2014-01-01

    The lysogenic state of the λ switch is exceptionally stable, still, it is capable of responding to DNA-damage and rapidly enter the lytic state. We invented an assay where PNA mediated tethering of a plasmid allowed for single molecule investigations of the effect of supercoiling on the efficiency...

  18. 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.

  19. 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

  20. 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...

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

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    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

  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. 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 ...

  4. 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.

  5. 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

  6. Lytic polysaccharide monooxygenases from Myceliophthora thermophila C1

    NARCIS (Netherlands)

    Frommhagen, Matthias

    2017-01-01

    Current developments aim at the effective enzymatic degradation of plant biomass polysaccharides into fermentable monosaccharides for biofuels and biochemicals. Recently discovered lytic polysaccharide monooxgygenases (LPMOs) boost the hydrolytic breakdown of lignocellulosic biomass, especially

  7. The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

    Directory of Open Access Journals (Sweden)

    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.

  8. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

    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.

  9. 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.

  10. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    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

  11. 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...

  12. 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

  13. [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.

  14. 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.

  15. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Painful Lytic Lesions of the Foot : A Case Report

    Directory of Open Access Journals (Sweden)

    R Vaishya

    2015-03-01

    Full Text Available The presence of lytic lesions in the bones of foot raises a number of diagnostic possibilities ranging from infection, inflammatory pathology to neoplastic conditions. Although the radiological picture is not pathognomonic of any pathology, clinical history and histopathological examination can help to clinch the diagnosis. We present a case of multiple lytic lesions of the foot and discuss possible differential diagnoses. The patient was diagnosed as a case of madura foot and the lesions responded to surgical debridement and anti-fungal treatment with a good functional outcome. Madura foot is an uncommon, chronic granulomatous fungal or bacterial infection with a predilection in people who walk barefoot. Although known for a specific geographical distribution, madura foot should be kept as a possible diagnosis in patients presenting with lytic lesions of the foot due to population emigration across the world.

  18. Metastatic Breast Cancer or Multiple Myeloma? Camouflage by Lytic Lesions

    Directory of Open Access Journals (Sweden)

    Bruce Hough

    2010-01-01

    Full Text Available We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.

  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. 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

  1. 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

  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. MUREIN-METABOLIZING ENZYMES FROM ESCHERICHIA-COLI - EXISTENCE OF A 2ND LYTIC TRANSGLYCOSYLASE

    NARCIS (Netherlands)

    ENGEL, H; SMINK, AJ; VANWIJNGAARDEN, L; KECK, W

    1992-01-01

    In addition to the soluble lytic transglycosylase, a murein-metabolizing enzyme with a molecular mass of 70 kDa (Slt70), Escherichia coli possesses a second lytic transglycosylase, which has been described as a membrane-bound lytic transglycosylase (Mlt; 35 kDa; EC 3.2.1.-). The mlt gene, which

  4. 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; Ackermann, Mathias; Balazs, George H.

    2017-01-01

    Fibropapillomatosis (FP) is a tumor disease of marine turtles associated with Chelonid herpesvirus 5 (ChHV5) that 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 for active lytic replication of the virus. The minimal requirements to achieve lytic replication in cultured cells included 1) either in-vitro culturing of ChHV5-positive tumor biopsies (plugs) or organotypic cultures (rafts) consisting of ChHV5-positive turtle fibroblasts in collagen rafts seeded with turtle keratinocytes and 2) keratinocyte maturation induced by raising raft or biopsy cultures to the air-liquid interface. Virus growth was confirmed by detailed electron microscopic studies revealing intranuclear sun-shaped capsid factories, tubules, various stages of capsid formation, nuclear export by budding into the perinuclear space, tegumentation, and envelopment to complete de novo virus production. Membrane synthesis was also observed as a sign for active viral replication. Interestingly, cytoplasmic particles became associated with keratin filaments, a feature not seen in conventional monolayer cell cultures where 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 model to culture other viruses that are resistant to replication in conventional cell culture.

  5. 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.)

  6. 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...

  7. 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.)

  8. Viral infection model with periodic lytic immune response

    International Nuclear Information System (INIS)

    Wang Kaifa; Wang Wendi; Liu Xianning

    2006-01-01

    Dynamical behavior and bifurcation structure of a viral infection model are studied under the assumption that the lytic immune response is periodic in time. The infection-free equilibrium is globally asymptotically stable when the basic reproductive ratio of virus is less than or equal to one. There is a non-constant periodic solution if the basic reproductive ratio of the virus is greater than one. It is found that period doubling bifurcations occur as the amplitude of lytic component is increased. For intermediate birth rates, the period triplication occurs and then period doubling cascades proceed gradually toward chaotic cycles. For large birth rate, the period doubling cascade proceeds gradually toward chaotic cycles without the period triplication, and the inverse period doubling can be observed. These results can be used to explain the oscillation behaviors of virus population, which was observed in chronic HBV or HCV carriers

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch

    DEFF Research Database (Denmark)

    Norregaard, Kamilla; Andersson, Magnus; Sneppen, Kim

    2013-01-01

    Bacteriophage λ stably maintains its dormant prophage state but efficiently enters lytic development in response to DNA damage. The mediator of these processes is the λ repressor protein, CI, and its interactions with λ operator DNA. This λ switch is a model on the basis of which epigenetic switch...... with relaxed DNA, the presence of supercoils greatly enhances juxtaposition probability. Also, the efficiency and cooperativity of the λ switch is significantly increased in the supercoiled system compared with a linear assay, increasing the Hill coefficient....

  12. 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.

  13. 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.

  14. 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.

  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. PMID

  16. 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.

  17. 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

  18. 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.

  19. [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.

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

    Science.gov (United States)

    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.

  1. 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

  2. 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.

  3. 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

  4. Bacteriophage lytic to Desulfovibrio aespoeensis isolated from deep groundwater.

    Science.gov (United States)

    Eydal, Hallgerd S C; Jägevall, Sara; Hermansson, Malte; Pedersen, Karsten

    2009-10-01

    Viruses were earlier found to be 10-fold more abundant than prokaryotes in deep granitic groundwater at the Aspö Hard Rock Laboratory (HRL). Using a most probable number (MPN) method, 8-30 000 cells of sulphate-reducing bacteria per ml were found in groundwater from seven boreholes at the Aspö HRL. The content of lytic phages infecting the indigenous bacterium Desulfovibrio aespoeensis in Aspö groundwater was analysed using the MPN technique for phages. In four of 10 boreholes, 0.2-80 phages per ml were found at depths of 342-450 m. Isolates of lytic phages were made from five cultures. Using transmission electron microscopy, these were characterized and found to be in the Podoviridae morphology group. The isolated phages were further analysed regarding host range and were found not to infect five other species of Desulfovibrio or 10 Desulfovibrio isolates with up to 99.9% 16S rRNA gene sequence identity to D. aespoeensis. To further analyse phage-host interactions, using a direct count method, growth of the phages and their host was followed in batch cultures, and the viral burst size was calculated to be approximately 170 phages per lytic event, after a latent period of approximately 70 h. When surviving cells from infected D. aespoeensis batch cultures were inoculated into new cultures and reinfected, immunity to the phages was found. The parasite-prey system found implies that viruses are important for microbial ecosystem diversity and activity, and for microbial numbers in deep subsurface groundwater.

  5. 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

  6. Percutaneous aspiration biopsy in cervical spine lytic lesions

    International Nuclear Information System (INIS)

    Tampieri, D.; Weill, A.; Melanson, D.; Ethier, R.

    1991-01-01

    We describe the technique and the results of the percutaneous aspiration biopsy (PAB) in a series of 9 patients presenting with neck pain and different degrees of myelopathy, in whom the cervical spine X-ray demonstrated lytic lesions of unknown origin. PAB is a useful, relatively safe technique, and leads to histological diagnosis between metastatic and inflammatory processes. Furthermore, in inflammatory lesions with negative hemoculture, PAB may help in detecting the micro-organism responsible and therefore allow a better antibiotic treatment. (orig.)

  7. Exciter switch

    Science.gov (United States)

    Mcpeak, W. L.

    1975-01-01

    A new exciter switch assembly has been installed at the three DSN 64-m deep space stations. This assembly provides for switching Block III and Block IV exciters to either the high-power or 20-kW transmitters in either dual-carrier or single-carrier mode. In the dual-carrier mode, it provides for balancing the two drive signals from a single control panel located in the transmitter local control and remote control consoles. In addition to the improved switching capabilities, extensive monitoring of both the exciter switch assembly and Transmitter Subsystem is provided by the exciter switch monitor and display assemblies.

  8. Immunology: Is Actin at the Lytic Synapse a Friend or a Foe?

    Science.gov (United States)

    Hammer, John A

    2018-02-19

    Cytotoxic T cells and natural killer cells defend us against disease by secreting lytic granules. Whether actin facilitates or thwarts lytic granule secretion has been an open question. Recent results now indicate that the answer depends on the maturation stage of the immune cell-target cell contact. Published by Elsevier Ltd.

  9. Lytic effects of mixed micelles of fatty acids and bile acids

    NARCIS (Netherlands)

    Lapré, J. A.; Termont, D. S.; Groen, A. K.; van der Meer, R.

    1992-01-01

    It has been hypothesized that bile acids and fatty acids promote colon cancer. A proposed mechanism is a lytic effect of these surfactants on colonic epithelium, resulting in a compensatory proliferation of colonic cells. To investigate the first step of this hypothesis, we studied the lytic

  10. Herpesviral ICP0 Protein Promotes Two Waves of Heterochromatin Removal on an Early Viral Promoter during Lytic Infection

    Directory of Open Access Journals (Sweden)

    Jennifer S. Lee

    2016-01-01

    Full Text Available Herpesviruses must contend with host cell epigenetic silencing responses acting on their genomes upon entry into the host cell nucleus. In this study, we confirmed that unchromatinized herpes simplex virus 1 (HSV-1 genomes enter primary human foreskin fibroblasts and are rapidly subjected to assembly of nucleosomes and association with repressive heterochromatin modifications such as histone 3 (H3 lysine 9-trimethylation (H3K9me3 and lysine 27-trimethylation (H3K27me3 during the first 1 to 2 h postinfection. Kinetic analysis of the modulation of nucleosomes and heterochromatin modifications over the course of lytic infection demonstrates a progressive removal that coincided with initiation of viral gene expression. We obtained evidence for three phases of heterochromatin removal from an early gene promoter: an initial removal of histones and heterochromatin not dependent on ICP0, a second ICP0-dependent round of removal of H3K9me3 that is independent of viral DNA synthesis, and a third phase of H3K27me3 removal that is dependent on ICP0 and viral DNA synthesis. The presence of ICP0 in transfected cells is also sufficient to promote removal of histones and H3K9me3 modifications of cotransfected genes. Overall, these results show that ICP0 promotes histone removal, a reduction of H3K9me3 modifications, and a later indirect reduction of H3K27me3 modifications following viral early gene expression and DNA synthesis. Therefore, HSV ICP0 promotes the reversal of host epigenetic silencing mechanisms by several mechanisms.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Pseudospark switches

    International Nuclear Information System (INIS)

    Billault, P.; Riege, H.; Gulik, M. van; Boggasch, E.; Frank, K.

    1987-01-01

    The pseudospark discharge is bound to a geometrical structure which is particularly well suited for switching high currents and voltages at high power levels. This type of discharge offers the potential for improvement in essentially all areas of switching operation: peak current and current density, current rise, stand-off voltage, reverse current capability, cathode life, and forward drop. The first pseudospark switch was built at CERN at 1981. Since then, the basic switching characteristics of pseudospark chambers have been studied in detail. The main feature of a pseudospark switch is the confinement of the discharge plasma to the device axis. The current transition to the hollow electrodes is spread over a rather large surface area. Another essential feature is the easy and precise triggering of the pseudospark switch from the interior of the hollow electrodes, relatively far from the main discharge gap. Nanosecond delay and jitter values can be achieved with trigger energies of less than 0.1 mJ, although cathode heating is not required. Pseudospark gaps may cover a wide range of high-voltage, high-current, and high-pulse-power switching at repetition rates of many kilohertz. This report reviews the basic researh on pseudospark switches which has been going on at CERN. So far, applications have been developed in the range of thyratron-like medium-power switches at typically 20 to 40 kV and 0.5 to 10 kA. High-current pseudospark switches have been built for a high-power 20 kJ pulse generator which is being used for long-term tests of plasma lenses developed for the future CERN Antiproton Collector (ACOL). The high-current switches have operated for several hundred thousand shots, with 20 to 50 ns jitter at 16 kV charging voltage and more than 100 kA peak current amplitude. (orig.)

  18. Characterization of newly isolated lytic bacteriophages active against Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Maia Merabishvili

    Full Text Available Based on genotyping and host range, two newly isolated lytic bacteriophages, myovirus vB_AbaM_Acibel004 and podovirus vB_AbaP_Acibel007, active against Acinetobacter baumannii clinical strains, were selected from a new phage library for further characterization. The complete genomes of the two phages were analyzed. Both phages are characterized by broad host range and essential features of potential therapeutic phages, such as short latent period (27 and 21 min, respectively, high burst size (125 and 145, respectively, stability of activity in liquid culture and low frequency of occurrence of phage-resistant mutant bacterial cells. Genomic analysis showed that while Acibel004 represents a novel bacteriophage with resemblance to some unclassified Pseudomonas aeruginosa phages, Acibel007 belongs to the well-characterized genus of the Phikmvlikevirus. The newly isolated phages can serve as potential candidates for phage cocktails to control A. baumannii infections.

  19. Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.

    Science.gov (United States)

    Kosowicz, John G; Lee, Jaeyeun; Peiffer, Brandon; Guo, Zufeng; Chen, Jianmeng; Liao, Gangling; Hayward, S Diane; Liu, Jun O; Ambinder, Richard F

    2017-08-15

    Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib. IMPORTANCE EBV establishes viral latency in B cells. Activation of the B cell receptor pathway activates lytic viral expression in cell lines. Here we show that drugs that inhibit important kinases in the BCR signaling pathway inhibit activation of lytic viral expression but do not inhibit several other lytic activation pathways. Immunosuppressant drugs such as cyclosporine and tacrolimus but not rapamycin also inhibit BCR-mediated EBV activation. Finally, we show that BCR activation of lytic infection occurs not only in tumor cell lines but also in freshly isolated B cells from patients and that this activation can be blocked by BCR inhibitors. Copyright © 2017 American Society for Microbiology.

  20. In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

    International Nuclear Information System (INIS)

    Rowe, Alexander M.; Brundage, Kathleen M.; Barnett, John B.

    2007-01-01

    The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4-h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine-treated cells than vehicle-treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells

  1. 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), ...

  2. 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.

  3. Human herpesvirus 8 – A novel human pathogen

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  5. 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.

  6. Potential of a lytic bacteriophage to disrupt Acinetobacter baumannii biofilms in vitro.

    Science.gov (United States)

    Liu, Yannan; Mi, Zhiqiang; Niu, Wenkai; An, Xiaoping; Yuan, Xin; Liu, Huiying; Wang, Yong; Feng, Yuzhong; Huang, Yong; Zhang, Xianglilan; Zhang, Zhiyi; Fan, Hang; Peng, Fan; Li, Puyuan; Tong, Yigang; Bai, Changqing

    2016-10-01

    The ability of Acinetobacter baumannii to form biofilms and develop antibiotic resistance makes it difficult to control infections caused by this bacterium. In this study, we explored the potential of a lytic bacteriophage to disrupt A. baumannii biofilms. The potential of the lytic bacteriophage to disrupt A. baumannii biofilms was assessed by performing electron microscopy, live/dead bacterial staining, crystal violet staining and by determining adenosine triphosphate release. The bacteriophage inhibited the formation of and disrupted preformed A. baumannii biofilms. Results of disinfection assay showed that the lytic bacteriophage lysed A. baumannii cells suspended in blood or grown on metal surfaces. These results suggest the potential of the lytic bacteriophage to disrupt A. baumannii biofilms.

  7. Navigating barriers: the challenge of directed secretion at the natural killer cell lytic immunological synapse.

    Science.gov (United States)

    Sanborn, Keri B; Orange, Jordan S

    2010-05-01

    Natural killer (NK) cells have an inherent ability to recognize and destroy a wide array of cells rendered abnormal by stress or disease. NK cells can kill a targeted cell by forming a tight interface-the lytic immunological synapse. This represents a dynamic molecular arrangement that over time progresses through a series of steps to ultimately deliver the contents of specialized organelles known as lytic granules. In order to mediate cytotoxicity, the NK cell faces the challenge of mobilizing the lytic granules, polarizing them to the targeted cell, facilitating their approximation to the NK cell membrane, and releasing their contents. This review is focused upon the final steps in accessing function through the lytic immunological synapse.

  8. 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.

  9. 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.

  10. Liposome Disruption Assay to Examine Lytic Properties of Biomolecules.

    Science.gov (United States)

    Jimah, John R; Schlesinger, Paul H; Tolia, Niraj H

    2017-08-05

    Proteins may have three dimensional structural or amino acid features that suggest a role in targeting and disrupting lipids within cell membranes. It is often necessary to experimentally investigate if these proteins and biomolecules are able to disrupt membranes in order to conclusively characterize the function of these biomolecules. Here, we describe an in vitro assay to evaluate the membrane lytic properties of proteins and biomolecules. Large unilamellar vesicles (liposomes) containing carboxyfluorescein at fluorescence-quenching concentrations are treated with the biomolecule of interest. A resulting increase in fluorescence due to leakage of the dye from liposomes and subsequent dilution in the buffer demonstrates that the biomolecule is sufficient for disrupting liposomes and membranes. Additionally, since liposome disruption may occur via pore-formation or via general solubilization of lipids similar to detergents, we provide a method to distinguish between these two mechanisms. Pore-formation can be identified and evaluated by examining the blockade of carboxyfluorescein release with dextran molecules that fit the pore. The methods described here were used to determine that the malaria vaccine candidate CelTOS and proapoptotic Bax disrupt liposomes by pore formation (Saito et al. , 2000; Jimah et al. , 2016). Since membrane lipid binding by a biomolecule precedes membrane disruption, we recommend the companion protocol: Jimah et al. , 2017.

  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. 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.

  13. 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.

  14. Discovery and industrial applications of lytic polysaccharide mono-oxygenases.

    Science.gov (United States)

    Johansen, Katja S

    2016-02-01

    The recent discovery of copper-dependent lytic polysaccharide mono-oxygenases (LPMOs) has opened up a vast area of research covering several fields of application. The biotech company Novozymes A/S holds patents on the use of these enzymes for the conversion of steam-pre-treated plant residues such as straw to free sugars. These patents predate the correct classification of LPMOs and the striking synergistic effect of fungal LPMOs when combined with canonical cellulases was discovered when fractions of fungal secretomes were evaluated in industrially relevant enzyme performance assays. Today, LPMOs are a central component in the Cellic CTec enzyme products which are used in several large-scale plants for the industrial production of lignocellulosic ethanol. LPMOs are characterized by an N-terminal histidine residue which, together with an internal histidine and a tyrosine residue, co-ordinates a single copper atom in a so-called histidine brace. The mechanism by which oxygen binds to the reduced copper atom has been reported and the general mechanism of copper-oxygen-mediated activation of carbon is being investigated in the light of these discoveries. LPMOs are widespread in both the fungal and the bacterial kingdoms, although the range of action of these enzymes remains to be elucidated. However, based on the high abundance of LPMOs expressed by microbes involved in the decomposition of organic matter, the importance of LPMOs in the natural carbon-cycle is predicted to be significant. In addition, it has been suggested that LPMOs play a role in the pathology of infectious diseases such as cholera and to thus be relevant in the field of medicine. © 2016 Authors; published by Portland Press Limited.

  15. HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.

    Directory of Open Access Journals (Sweden)

    Emi Sei

    2015-02-01

    Full Text Available The Kaposi's sarcoma associated herpesvirus (KSHV is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL, and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP. As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5' ends. The position of these 5'-bound fragments correlated closely with the 5'-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9 and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

  16. 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.

  17. Switching Phenomena

    Science.gov (United States)

    Stanley, H. E.; Buldyrev, S. V.; Franzese, G.; Havlin, S.; Mallamace, F.; Mazza, M. G.; Kumar, P.; Plerou, V.; Preis, T.; Stokely, K.; Xu, L.

    One challenge of biology, medicine, and economics is that the systems treated by these serious scientific disciplines can suddenly "switch" from one behavior to another, even though they possess no perfect metronome in time. As if by magic, out of nothing but randomness one finds remarkably fine-tuned processes in time. The past century has, philosophically, been concerned with placing aside the human tendency to see the universe as a fine-tuned machine. Here we will address the challenge of uncovering how, through randomness (albeit, as we shall see, strongly correlated randomness), one can arrive at some of the many temporal patterns in physics, economics, and medicine and even begin to characterize the switching phenomena that enable a system to pass from one state to another. We discuss some applications of correlated randomness to understanding switching phenomena in various fields. Specifically, we present evidence from experiments and from computer simulations supporting the hypothesis that water's anomalies are related to a switching point (which is not unlike the "tipping point" immortalized by Malcolm Gladwell), and that the bubbles in economic phenomena that occur on all scales are not "outliers" (another Gladwell immortalization).

  18. 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...

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

    Directory of Open Access Journals (Sweden)

    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. 

  20. Hypoxia-inducible factor-1α plays roles in Epstein-Barr virus's natural life cycle and tumorigenesis by inducing lytic infection through direct binding to the immediate-early BZLF1 gene promoter.

    Directory of Open Access Journals (Sweden)

    Richard J Kraus

    2017-06-01

    Full Text Available When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs. We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV. Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens. ShRNA knockdown of HIF-1α significantly reduced deferoxamine-mediated lytic reactivation. HIF-1α directly bound the promoter of the EBV primary latent-lytic switch BZLF1 gene, Zp, activating transcription via a consensus hypoxia-response element (HRE located at nt -83 through -76 relative to the transcription initiation site. HIF-1α did not activate transcription from the other EBV immediate-early gene, BRLF1. Importantly, expression of HIF-1α induced EBV lytic-gene expression in cells harboring wild-type EBV, but not in cells infected with variants containing base-pair substitution mutations within this HRE. Human oral keratinocyte (NOK and gingival epithelial (hGET cells induced to differentiate by incubation with either methyl cellulose or growth in organotypic culture accumulated both HIF-1α and Blimp-1α, another cellular factor implicated in lytic reactivation. HIF-1α activity also accumulated along with Blimp-1α during B-cell differentiation into plasma cells. Furthermore, most BZLF1-expressing cells observed in lymphomas induced by EBV in NSG mice with a humanized immune system were located distal to blood vessels in hypoxic regions of the tumors. Thus, we conclude that HIF-1α plays central roles in both EBV's natural life cycle and EBV-associated tumorigenesis. We propose that drugs that induce HIF-1α protein accumulation are good candidates for

  1. 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

  2. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.

    Science.gov (United States)

    Yosef, Ido; Manor, Miriam; Kiro, Ruth; Qimron, Udi

    2015-06-09

    The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.

  3. The Lytic SA Phage Demonstrate Bactericidal Activity against Mastitis Causing Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Hamza Ameer

    2016-01-01

    Full Text Available Staphylococcus aureus is the major causative agent of mastitis among dairy animals as it causes intramammary gland infection. Due to antibiotic resistance and contamination of antibiotics in the milk of diseased animals; alternative therapeutic agents are required to cure mastitis. Lytic bacteriophages and their gene products can be potential therapeutic agents against bacteria as they are host specific and less harmful than antibiotics. In this study, Staphylococcus aureus were isolated from milk samples of the infected animals and identified biochemically. SA phage was isolated from sewage water showing lytic activity against Staphylococcus aureus isolates. The highest lytic activity of bacteriophages was observed at 37°C and pH 7, and the most suitable storage condition was at 4°C. SA phage efficiently reduced bacterial growth in the bacterial reduction assay. The characterization and bacterial growth reduction activity of the bacteriophages against Staphylococcus aureus signifies their underlying potential of phage therapy against mastitis.

  4. The importance of lytic and nonlytic immune responses in viral infections

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2002-01-01

    Antiviral immune effector mechanisms can be divided broadly into lytic and nonlytic components. We use mathematical models to investigate the fundamental question of which type of response is required to combat different types of viral infection. According to our model, the relative roles...... of the two types of component depend on the cytopathicity of the virus relative to its rate of replication. If the viral cytopathicity is low relative to the rate of viral replication, the model predicts that a combination of lytic and nonlytic effector mechanisms is likely to be required to resolve...

  5. Phenoloxidase but not lytic activity reflects resistance against Pasteuria ramosa in Daphnia magna.

    Science.gov (United States)

    Pauwels, Kevin; De Meester, Luc; Decaestecker, Ellen; Stoks, Robby

    2011-02-23

    The field of ecological immunology strongly relies on indicators of immunocompetence. Two major indicators in invertebrates, the activity of phenoloxidase (PO) and lytic activity have recently been questioned in studies showing that, across a natural range of baseline levels, these indicators did not predict resistance against a manipulated challenge with natural parasites. We confirmed this finding by showing that baseline levels of PO and lytic activity in the host Daphnia magna were not related to spore load of the parasite Pasteuria ramosa. Yet, PO levels in infected hosts did predict spore load, indicating PO activity can be useful as an indicator of immunocompetence in this model parasite-host system.

  6. 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 ...

  7. 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

  8. 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

  9. 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 ...

  10. 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...

  11. 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...

  12. 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

  13. 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.

  14. 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...

  15. Effectiveness of lytic bacteriophages in reducing E. coli O157:H7 populations introduced through cross-contamination on fresh cut lettuce

    Science.gov (United States)

    Previous research has shown that lytic bacteriophages (phages) can kill E. coli O157:H7 on produce surfaces. The role of lytic bacteriophages in preventing cross contamination of produce has not been evaluated. A cocktail of three lytic phages specific for E. coli O157:H7 (EcoShield) at 10^8 PFU/m...

  16. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    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

  17. Short-Chain Fatty Acids from Periodontal Pathogens Suppress Histone Deacetylases, EZH2, and SUV39H1 To Promote Kaposi's Sarcoma-Associated Herpesvirus Replication

    Science.gov (United States)

    Yu, Xiaolan; Shahir, Abdel-Malek; Sha, Jingfeng; Feng, Zhimin; Eapen, Betty; Nithianantham, Stanley; Das, Biswajit; Karn, Jonathan; Weinberg, Aaron; Bissada, Nabil F.

    2014-01-01

    ABSTRACT Periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum produce five different short-chain fatty acids (SCFAs) as metabolic by-products. We detect significantly higher levels of SCFAs in the saliva of patients with severe periodontal disease. The different SCFAs stimulate lytic gene expression of Kaposi's sarcoma-associated herpesvirus (KSHV) dose dependently and synergistically. SCFAs inhibit class-1/2 histone deacetylases (HDACs) and downregulate expression of silent information regulator-1 (SIRT1). SCFAs also downregulate expression of enhancer of zeste homolog2 (EZH2) and suppressor of variegation 3-9 homolog1 (SUV39H1), which are two histone N-lysine methyltransferases (HLMTs). By suppressing the different components of host epigenetic regulatory machinery, SCFAs increase histone acetylation and decrease repressive histone trimethylations to transactivate the viral chromatin. These new findings provide mechanistic support that SCFAs from periodontal pathogens stimulate KSHV replication and infection in the oral cavity and are potential risk factors for development of oral Kaposi's sarcoma (KS). IMPORTANCE About 20% of KS patients develop KS lesions first in the oral cavity, while other patients never develop oral KS. It is not known if the oral microenvironment plays a role in oral KS tumor development. In this work, we demonstrate that a group of metabolic by-products, namely, short-chain fatty acids, from bacteria that cause periodontal disease promote lytic replication of KSHV, the etiological agent associated with KS. These new findings provide mechanistic support that periodontal pathogens create a unique microenvironment in the oral cavity that contributes to KSHV replication and development of oral KS. PMID:24501407

  18. Hemoglobin is a co-factor of human trypanosome lytic factor

    DEFF Research Database (Denmark)

    Widener, Justin; Nielsen, Marianne Jensby; Shiflett, April

    2007-01-01

    Trypanosome lytic factor (TLF) is a high-density lipoprotein (HDL) subclass providing innate protection to humans against infection by the protozoan parasite Trypanosoma brucei brucei. Two primate-specific plasma proteins, haptoglobin-related protein (Hpr) and apolipoprotein L-1 (ApoL-1), have be...

  19. Role of the adenovirus early region 1B tumor antigens in transformation and lytic infection

    NARCIS (Netherlands)

    Bernards, R.A.; Leeuw, M.G.W. de; Houweling, A.; Eb, A.J. van der

    1986-01-01

    We have investigated the contribution of each of the two adenovirus type 5 (Ad5) major early region lb (Elb) proteins in cell transformation and in lytic infection. An Ad5 El plasmid, in which the reading frame for the 19-kDa Elb protein was abolished by a stop codon close to the initiation codon,

  20. Crystal structure and mechanism of the lytic transglycosylase MltA from Escherichia coli

    NARCIS (Netherlands)

    van Straaten, Karin

    2006-01-01

    This thesis describes the determination and analysis of the 3D-structure of the lytic transglycosylase MltA from Escherichia coli by X-ray crystallography. This work aims to further increase our knowledge of the molecular details of the cleaving mechanism and the typical 1,6- anhydromuropeptide

  1. Analyzing Activities of Lytic Polysaccharide Monooxygenases by Liquid Chromatography and Mass Spectrometry

    DEFF Research Database (Denmark)

    Westereng, Bjørge; Arntzen, Magnus Ø.; Wittrup Agger, Jane

    2017-01-01

    Lytic polysaccharide monooxygenases perform oxidative cleavage of glycosidic bonds in various polysaccharides. The majority of LMPOs studied so far possess activity on either cellulose or chitin and analysis of these activities is therefore the main focus of this review. Notably, however, the num...

  2. Genetic characterization of ØVC8 lytic phage for Vibrio cholerae O1.

    Science.gov (United States)

    Solís-Sánchez, Alejandro; Hernández-Chiñas, Ulises; Navarro-Ocaña, Armando; De la Mora, Javier; Xicohtencatl-Cortes, Juan; Eslava-Campos, Carlos

    2016-03-22

    Epidemics and pandemics of cholera, a diarrheal disease, are attributed to Vibrio cholera serogroups O1 and O139. In recent years, specific lytic phages of V. cholera have been proposed to be important factors in the cyclic occurrence of cholera in endemic areas. However, the role and potential participation of lytic phages during long interepidemic periods of cholera in non-endemic regions have not yet been described. The purpose of this study was to isolate and characterize specific lytic phages of V. cholera O1 strains. Sixteen phages were isolated from wastewater samples collected at the Endhó Dam in Hidalgo State, Mexico, concentrated with PEG/NaCl, and purified by density gradient. The lytic activity of the purified phages was tested using different V. cholerae O1 and O139 strains. Phage morphology was visualized by transmission electron microscopy (TEM), and phage genome sequencing was performed using the Genome Analyzer IIx System. Genome assembly and bioinformatics analysis were performed using a set of high-throughput programs. Phage structural proteins were analyzed by mass spectrometry. Sixteen phages with lytic and lysogenic activity were isolated; only phage ØVC8 showed specific lytic activity against V. cholerae O1 strains. TEM images of ØVC8 revealed a phage with a short tail and an isometric head. The ØVC8 genome comprises linear double-stranded DNA of 39,422 bp with 50.8 % G + C. Of the 48 annotated ORFs, 16 exhibit homology with sequences of known function and several conserved domains. Bioinformatics analysis showed multiple conserved domains, including an Ig domain, suggesting that ØVC8 might adhere to different mucus substrates such as the human intestinal epithelium. The results suggest that ØVC8 genome utilize the "single-stranded cohesive ends" packaging strategy of the lambda-like group. The two structural proteins sequenced and analyzed are proteins of known function. ØVC8 is a lytic phage with specific activity against V. cholerae

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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 microRNAs

    Directory of Open Access Journals (Sweden)

    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. In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas)

    Science.gov (United States)

    Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Schumacher, Joanne; Lewis, Teresa D.; Leong, Jo-Ann C.; Casey, Rufina N.; Casey, James W.

    2009-01-01

    Fibropapillomatosis (FP) of green turtles has a global distribution and causes debilitating tumours of the skin and internal organs in several species of marine turtles. FP is associated with a presently non-cultivable alphaherpesvirus Chelonid fibropapilloma-associated herpesvirus (CFPHV). Our aims were to employ quantitative PCR targeted to pol DNA of CFPHV to determine (i) if DNA sequesters by tumour size and/or cell type, (ii) whether subculturing of cells is a viable strategy for isolating CFPHV and (iii) whether CFPHV can be induced to a lytic growth cycle in vitro using chemical modulators of replication (CMRs), temperature variation or co-cultivation. Additional objectives included determining whether non-tumour and tumour cells behave differently in vitro and confirming the phenotype of cultured cells using cell-type-specific antigens. CFPHV pol DNA was preferentially concentrated in dermal fibroblasts of skin tumours and the amount of viral DNA per cell was independent of tumour size. Copy number of CFPHV pol DNA per cell rapidly decreased with cell doubling of tumour-derived fibroblasts in culture. Attempts to induce viral replication in known CFPHV-DNA-positive cells using temperature or CMR failed. No significant differences were seen in in vitro morphology or growth characteristics of fibroblasts from tumour cells and paired normal skin, nor from CFPHV pol-DNA-positive intestinal tumour cells. Tumour cells were confirmed as fibroblasts or keratinocytes by positive staining with anti-vimentin and anti-pancytokeratin antibodies, respectively. CFPHV continues to be refractory to in vitro cultivation.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Switched on!

    CERN Multimedia

    2008-01-01

    Like a star arriving on stage, impatiently followed by each member of CERN personnel and by millions of eyes around the world, the first beam of protons has circulated in the LHC. After years in the making and months of increasing anticipation, today the work of hundreds of people has borne fruit. WELL DONE to all! Successfully steered around the 27 kilometres of the world’s most powerful particle accelerator at 10:28 this morning, this first beam of protons circulating in the ring marks a key moment in the transition from over two decades of preparation to a new era of scientific discovery. "It’s a fantastic moment," said the LHC project leader Lyn Evans, "we can now look forward to a new era of understanding about the origins and evolution of the universe". Starting up a major new particle accelerator takes much more than flipping a switch. Thousands of individual elements have to work in harmony, timings have to be synchronize...

  18. 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.

  19. 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

  20. 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.

  1. A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus (KSHV) induces apoptosis, which is blocked in KSHV-infected cells

    International Nuclear Information System (INIS)

    Nishimura, Ken; Ueda, Keiji; Sakakibara, Shuhei; Do, Eunju; Ohsaki, Eriko; Okuno, Toshiomi; Yamanishi, Koichi

    2003-01-01

    Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50, is expressed in the immediate-early phase of reactivation and plays a critical role in inducing the viral lytic cycle in KSHV-infected cells. We established cell clones from BJAB cells and replication-deficient BCBL-1 cells in which KSHV RTA expression was controlled by an inducible promoter of the tetracycline-based Tet-Off expression system. In RTA-inducible BJAB cells, tetracycline removal induced the synthesis of RTA, resulting in cell death. DNA fragmentation, structural changes in the cell membrane, and poly(ADP-ribose) polymerase (PARP) cleavage were observed in the RTA-induced BJAB cells, indicating that RTA expression induced caspase activation and cell death by apoptosis. However, expression of RTA in RTA-inducible BCBL-1 cells did not undergo apoptosis and cell death. These results suggested that KSHV RTA is an apoptosis inducer that is opposed by an antiapoptotic pathway in infected cells

  2. Detection of Herpesvirus anguillae (AngHV-1) in European eel Anguilla anguilla (L.) originating from northern Poland-assessment of suitability of selected diagnostic methods.

    Science.gov (United States)

    Nguyen, Tuan Thuc; Jin, Yeonhwa; Kiełpińska, Jolanta; Bergmann, Sven M; Lenk, Matthias; Panicz, Remigiusz

    2017-11-01

    The Community Action Plan requests EU member states to implement measures that ensure the recovery of the severely depleted European eel stocks. One of the main threats is posed by Anguillid herpesvirus 1 (AngHV-1) leading to increased mortality in both wild and farmed eels. Following recommendations of the OIE to minimize the risk of obtaining false-negative results, the main aim of the study was to optimize diagnostic methods for AngHV-1 detection using conventional PCR, nested PCR and in situ hybridization assay. While 53.3% of the individual organ samples were tested positive for AngHV-1 by PCR, the additional virus analysis via nested PCR revealed that the actual prevalence was 93.3%. In the cell cultivation passages, a cytopathic effect was hardly found in the first two rounds. In the third passage onto cell cultures, a lytic CPE was detected. The identification and confirmation of the viruses obtained from cell cultures as well as directly from the organ tissues were proceeded by PCR, nested PCR and sequencing of the PCR products. While no positive signal was detectable in the first round by PCR using samples from the third cell culture passages, the nested PCR provided weak but visible positive signals. © 2017 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection.

    Science.gov (United States)

    Chijioke, Obinna; Müller, Anne; Feederle, Regina; Barros, Mario Henrique M; Krieg, Carsten; Emmel, Vanessa; Marcenaro, Emanuela; Leung, Carol S; Antsiferova, Olga; Landtwing, Vanessa; Bossart, Walter; Moretta, Alessandro; Hassan, Rocio; Boyman, Onur; Niedobitek, Gerald; Delecluse, Henri-Jacques; Capaul, Riccarda; Münz, Christian

    2013-12-26

    Primary infection with the human oncogenic Epstein-Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion that predisposes for the development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas the majority acquires the virus asymptomatically, remains unclear. Using a mouse model with reconstituted human immune system components, we show that depletion of human natural killer (NK) cells enhances IM symptoms and promotes EBV-associated tumorigenesis mainly because of a loss of immune control over lytic EBV infection. These data suggest that failure of innate immune control by human NK cells augments symptomatic lytic EBV infection, which drives lymphocyte expansion and predisposes for EBV-associated malignancies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Human Natural Killer Cells Prevent Infectious Mononucleosis Features by Targeting Lytic Epstein-Barr Virus Infection

    Directory of Open Access Journals (Sweden)

    Obinna Chijioke

    2013-12-01

    Full Text Available Primary infection with the human oncogenic Epstein-Barr virus (EBV can result in infectious mononucleosis (IM, a self-limiting disease caused by massive lymphocyte expansion that predisposes for the development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas the majority acquires the virus asymptomatically, remains unclear. Using a mouse model with reconstituted human immune system components, we show that depletion of human natural killer (NK cells enhances IM symptoms and promotes EBV-associated tumorigenesis mainly because of a loss of immune control over lytic EBV infection. These data suggest that failure of innate immune control by human NK cells augments symptomatic lytic EBV infection, which drives lymphocyte expansion and predisposes for EBV-associated malignancies.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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 ...

  11. Characteristics of a broad lytic spectrum endolysin from phage BtCS33 of Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Yuan Yihui

    2012-12-01

    Full Text Available Abstract Background Endolysins produced by bacteriophages lyse bacteria, and are thus considered a novel type of antimicrobial agent. Several endolysins from Bacillus phages or prophages have previously been characterized and used to target Bacillus strains that cause disease in animals and humans. B. thuringiensis phage BtCS33 is a Siphoviridae family phage and its genome has been sequenced and analyzed. In the BtCS33 genome, orf18 was found to encode an endolysin protein (PlyBt33. Results Bioinformatic analyses showed that endolysin PlyBt33 was composed of two functional domains, the N-terminal catalytic domain and the C-terminal cell wall binding domain. In this study, the entire endolysin PlyBt33, and both the N- and C-termini,were expressed in Escherichia coli and then purified. The lytic activities of PlyBt33 and its N-terminus were tested on bacteria. Both regions exhibited lytic activity, although PlyBt33 showed a higher lytic activity than the N-terminus. PlyBt33 exhibited activity against all Bacillus strains tested from five different species, but was not active against Gram-negative bacteria. Optimal conditions for PlyBt33 reactivity were pH 9.0 and 50°C. PlyBt33 showed high thermostability, with 40% of initial activity remaining following 1 h of treatment at 60°C. The C-terminus of PlyBt33 bound to B. thuringiensis strain HD-73 and Bacillus subtilis strain 168. This cell wall binding domain might be novel, as its amino acid sequence showed little similarity to previously reported endolysins. Conclusions PlyBt33 showed potential as a novel antimicrobial agent at a relatively high temperature and had a broad lytic spectrum within the Bacillus genus. The C-terminus of PlyBt33 might be a novel kind of cell wall binding domain.

  12. Digital switched hydraulics

    Science.gov (United States)

    Pan, Min; Plummer, Andrew

    2018-06-01

    This paper reviews recent developments in digital switched hydraulics particularly the switched inertance hydraulic systems (SIHSs). The performance of SIHSs is presented in brief with a discussion of several possible configurations and control strategies. The soft switching technology and high-speed switching valve design techniques are discussed. Challenges and recommendations are given based on the current research achievements.

  13. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  14. Diversity of phage infection types and associated terminology: the problem with 'Lytic or lysogenic'.

    Science.gov (United States)

    Hobbs, Zack; Abedon, Stephen T

    2016-04-01

    Bacteriophages, or phages, are viruses of members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective, these especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections versus lysogeny, pseudolysogeny and/or the phage carrier state), (2) the means of virion release (lytic versus chronic release) and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate versus non-temperate phages). We address in particular the use or overuse of what can be a somewhat equivocal phrase, 'Lytic or lysogenic', especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between 'Lytic' versus 'Lysogenic' phage types. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.

    Science.gov (United States)

    Talento, A; Nguyen, M; Law, S; Wu, J K; Poe, M; Blake, J T; Patel, M; Wu, T J; Manyak, C L; Silberklang, M

    1992-12-15

    Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.

  16. Are Phage Lytic Proteins the Secret Weapon To Kill Staphylococcus aureus?

    Directory of Open Access Journals (Sweden)

    Diana Gutiérrez

    2018-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of S. aureus include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs] have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in S. aureus animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against S. aureus infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials.

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

    DEFF Research Database (Denmark)

    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...

  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. Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

    Science.gov (United States)

    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

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. Latching micro optical switch

    Science.gov (United States)

    Garcia, Ernest J; Polosky, Marc A

    2013-05-21

    An optical switch reliably maintains its on or off state even when subjected to environments where the switch is bumped or otherwise moved. In addition, the optical switch maintains its on or off state indefinitely without requiring external power. External power is used only to transition the switch from one state to the other. The optical switch is configured with a fixed optical fiber and a movable optical fiber. The movable optical fiber is guided by various actuators in conjunction with a latching mechanism that configure the switch in one position that corresponds to the on state and in another position that corresponds to the off state.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

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

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    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.

  14. 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.

  15. 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.

  16. 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.

  17. A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion.

    Science.gov (United States)

    Liu, Yuehong; Li, Shufeng

    2015-01-01

    Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.

  18. Are Phage Lytic Proteins the Secret Weapon To Kill Staphylococcus aureus?

    Science.gov (United States)

    Gutiérrez, Diana; Fernández, Lucía; Rodríguez, Ana; García, Pilar

    2018-01-23

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of S. aureus include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in S. aureus animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against S. aureus infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials. Copyright © 2018 Gutiérrez et al.

  19. Noncanonical microRNAs and endogenous siRNAs in lytic infection of murine gammaherpesvirus.

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    Jing Xia

    Full Text Available MicroRNA (miRNA and endogenous small interfering RNA (endo-siRNA are two essential classes of small noncoding RNAs (sncRNAs in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68 (MHV68. In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from transfer RNAs, small nucleolar RNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from that of canonical miRNAs in lengths of hairpins, base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to produce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs. Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data and virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative targets of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new light on their potential functions of lytic infection of MHV68.

  20. Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Schils, Jean [Cleveland Clinic, Musculoskeletal Radiology, Cleveland, OH (United States); Joyce, Michael [Cleveland Clinic, Orthopedic Oncology, Cleveland, OH (United States); Shah, Chirag [Cleveland Clinic, Radiation Oncology, Cleveland, OH (United States); Zhang, Yaxia [Cleveland Clinic, Pathology, Cleveland, OH (United States)

    2017-11-15

    Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation. (orig.)

  1. Percutaneous aspiration biopsy in cervical spine lytic lesions. Indications and technique

    Energy Technology Data Exchange (ETDEWEB)

    Tampieri, D; Weill, A; Melanson, D; Ethier, R [Montreal Neurological Inst. and Hospital, PQ (Canada). Dept. of Neuroradiology

    1991-02-01

    We describe the technique and the results of the percutaneous aspiration biopsy (PAB) in a series of 9 patients presenting with neck pain and different degrees of myelopathy, in whom the cervical spine X-ray demonstrated lytic lesions of unknown origin. PAB is a useful, relatively safe technique, and leads to histological diagnosis between metastatic and inflammatory processes. Furthermore, in inflammatory lesions with negative hemoculture, PAB may help in detecting the micro-organism responsible and therefore allow a better antibiotic treatment. (orig.).

  2. 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.

  3. Protozoacidal Trojan-Horse: use of a ligand-lytic peptide for selective destruction of symbiotic protozoa within termite guts.

    Science.gov (United States)

    Sethi, Amit; Delatte, Jennifer; Foil, Lane; Husseneder, Claudia

    2014-01-01

    For novel biotechnology-based termite control, we developed a cellulose bait containing freeze-dried genetically engineered yeast which expresses a protozoacidal lytic peptide attached to a protozoa-recognizing ligand. The yeast acts as a 'Trojan-Horse' that kills the cellulose-digesting protozoa in the termite gut, which leads to the death of termites, presumably due to inefficient cellulose digestion. The ligand targets the lytic peptide specifically to protozoa, thereby increasing its protozoacidal efficiency while protecting non-target organisms. After ingestion of the bait, the yeast propagates in the termite's gut and is spread throughout the termite colony via social interactions. This novel paratransgenesis-based strategy could be a good supplement for current termite control using fortified biological control agents in addition to chemical insecticides. Moreover, this ligand-lytic peptide system could be used for drug development to selectively target disease-causing protozoa in humans or other vertebrates.

  4. 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

  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. Effect of metals on the lytic cycle of the coccolithovirus, EhV86.

    Directory of Open Access Journals (Sweden)

    Martha eGledhill

    2012-04-01

    Full Text Available In this study we show that metals, and in particular copper (Cu, can disrupt the lytic cycle in the Emiliania huxleyi - EhV86 host-virus system. Numbers of virus particles produced per E. huxleyi cell and E. huxleyi lysis rates were reduced by Cu at total metal concentrations over 500 nM in the presence of EDTA (ethylenediaminetetraacetic acid, and 250 nM in the absence of EDTA in acute short term exposure experiments. Zinc (Zn, cadmium (Cd and cobalt (Co were not observed to affect the lysis rate of EhV86 in these experiments. The cellular glutathione (GSH content increased in virus infected cells, but not as a result of metal exposure. In contrast, the cellular content of phytochelatins (PCs increased only in response to metal exposure. The increase in gluthatione content is consistent with increases in the production of reactive oxygen species (ROS on viral infection, while increases in PC content are likely linked to metal homeostasis and indicate that metal toxicity to the host was not affected by viral infection. We propose that Cu prevents lytic production of EhV86 by interfering with virus DNA (deoxyribonucleic acid synthesis through a transcriptional block, which ultimately suppresses the formation of ROS, a biochemical response required for successful virus infection.

  10. Characterization and lytic activity of methicillin-resistant Staphylococcus aureus(MRSA phages isolated from NICU

    Directory of Open Access Journals (Sweden)

    Golnar Rahimzadeh

    2016-06-01

    Full Text Available Background Methicillin-resistant Staphylococcus aureus (MRSA is a well-known pathogen that causes serious diseases in humans. As part of the efforts to control this pathogen, an isolated bacteriophage, Siphoviridae, which specifically targets Methicillin-resistant Staphylococcus aureus (MRSA, was characterized. Aims The objective of this study was to characterize of a virulent bacteriophage (Siphoviridae isolated from a NICU bathroom sink. Methods The MRSA strain was isolated from patient blood. The isolated strain was confirmed as MRSA using conventional methods. Phages were isolated from a NICU bathroom sink and activity was lytic as determined by spot test. Titer phage lysate was measured by the Double Layer Agar (DLA technique. The morphology was found with electron microscopy. The single-step growth curve was plotted. Results Electron microscopy showed the phage as a member of the family Siphoviridae, serogroup A and F. The isolated phage was capable of lytic activity against methicillin-resistant Staphylococcus aureus (MRSA strain as shown by spot test. By DLA, the titre of the phages was determined to be 10×108PFU/ml. The single-step growth curve showed that the latent period of the isolated bacteriophage was 30 min and the total number of viable progeny per infected host, burst size, was 2600 PFU/infected host. Conclusion In this study, two phages were isolated and characterized from a NICU bathroom sink, from the Siphoviridae family, which specifically targetsmethicillin-resistant Staphylococcus aureus (MRSA.

  11. PARTIAL CHARACTERIZATION OF A LYTIC METHICILLIN RESISTANT-STAPHYLOCOCCUS AUREUS BACTERIOPHAGE

    Directory of Open Access Journals (Sweden)

    Sulaiman Al-Yousef

    2014-12-01

    Full Text Available A marked increase in the infection incidence caused by methicillin-resistant Staphylococcus aureus (MRSA strains has been noted in medical practice in recent years. This study was conducted to study the biological and characterize of MRSA-phage. Methicillin resistance of Staphylococcus aureus was detected and confirmed by determining of the MIC of oxacillin by the standard agar dilution method. Phage was biologically purified using single plaque technique, then phage characterization were studied using host range, adsorption time, particle morphology and its structural protein. MRSA phage showing lytic nature was purified by repeated plating after picking of single isolated plaques. This phage is active against all 11 isolates either of S. aureus or MRSA tested as hosts. Phage produced clear plaques indicating their lytic nature. This phage was concentrated employing polyethylene glycol (PEG-NaCl precipitation method. Morphologically, MRSA Phage has a hexagonal head having a long non-contractile tail, indicating his icosahedral nature. Adsorption studies showed 100% adsorption of MRSA-Phage after 35 minutes of exposure. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE experimentation indicated that the phage particles contain one major structural protein (about 30 Kda.

  12. Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke--case report and literature review.

    LENUS (Irish Health Repository)

    O'Connell, David

    2011-01-01

    The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature.

  13. The use of lytic bacteriophages to reduce E. coli O157:H7 on fresh cut lettuce introduced through cross-contamination

    Science.gov (United States)

    The role of lytic bacteriophages in preventing cross contamination of produce has not been evaluated. A cocktail of three lytic phages specific for E. coli O157:H7 (EcoShield) at 108 PFU/ml or a control (phosphate buffered saline, PBS) was applied to lettuce by either 1) spraying on to lettuce piec...

  14. Augmentation of failed human vertebrae with critical un-contained lytic defect restores their structural competence under functional loading: An experimental study.

    Science.gov (United States)

    Alkalay, Ron N; von Stechow, Dietrich; Hackney, David B

    2015-07-01

    Lytic spinal lesions reduce vertebral strength and may result in their fracture. Vertebral augmentation is employed clinically to provide mechanical stability and pain relief for vertebrae with lytic lesions. However, little is known about its efficacy in strengthening fractured vertebrae containing lytic metastasis. Eighteen unembalmed human lumbar vertebrae, having simulated uncontained lytic defects and tested to failure in a prior study, were augmented using a transpedicular approach and re-tested to failure using a wedge fracture model. Axial and moment based strength and stiffness parameters were used to quantify the effect of augmentation on the structural response of the failed vertebrae. Effects of cement volume, bone mineral density and vertebral geometry on the change in structural response were investigated. Augmentation increased the failed lytic vertebral strength [compression: 85% (Paugmentation is effective in bolstering the failed lytic vertebrae compressive and axial structural competence, showing strength estimates up to 50-90% of historical values of osteoporotic vertebrae without lytic defects. This modest increase suggests that lytic vertebrae undergo a high degree of structural damage at failure, with strength only partially restored by vertebral augmentation. The positive effect of cement volume is self-limiting due to extravasation. Copyright © 2015. Published by Elsevier Ltd.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Optical packet switched networks

    DEFF Research Database (Denmark)

    Hansen, Peter Bukhave

    1999-01-01

    Optical packet switched networks are investigated with emphasis on the performance of the packet switch blocks. Initially, the network context of the optical packet switched network is described showing that a packet network will provide transparency, flexibility and bridge the granularity gap...... in interferometric wavelength converters is investigated showing that a 10 Gbit/s 19 4x4 swich blocks can be cascaded at a BER of 10-14. An analytical traffic model enables the calculation of the traffice performance of a WDM packet network. Hereby the importance of WDM and wavelegth conversion in the switch blocks...... is established as a flexible means to reduce the optical buffer, e.g., the number of fibre delay lines for a 16x16 switch block is reduced from 23 to 6 by going from 2 to 8 wavelength channels pr. inlet. Additionally, a component count analysis is carried out to illustrate the trade-offs in the switch block...

  5. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah

    2012-01-01

    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  6. Effective switching frequency multiplier inverter

    Science.gov (United States)

    Su, Gui-Jia [Oak Ridge, TN; Peng, Fang Z [Okemos, MI

    2007-08-07

    A switching frequency multiplier inverter for low inductance machines that uses parallel connection of switches and each switch is independently controlled according to a pulse width modulation scheme. The effective switching frequency is multiplied by the number of switches connected in parallel while each individual switch operates within its limit of switching frequency. This technique can also be used for other power converters such as DC/DC, AC/DC converters.

  7. FreeSWITCH Cookbook

    CERN Document Server

    Minessale, Anthony

    2012-01-01

    This is a problem-solution approach to take your FreeSWITCH skills to the next level, where everything is explained in a practical way. If you are a system administrator, hobbyist, or someone who uses FreeSWITCH on a regular basis, this book is for you. Whether you are a FreeSWITCH expert or just getting started, this book will take your skills to the next level.

  8. Elements of magnetic switching

    International Nuclear Information System (INIS)

    Aaland, K.

    1983-01-01

    This chapter describes magnetic switching as a method of connecting a capacitor bank (source) to a load; reviews several successful applications of magnetic switching, and discusses switching transformers, limitations and future possibilities. Some of the inflexibility and especially the high cost of magnetic materials may be overcome with the availability of the new splash cooled ribbons (Metglas). Experience has shown that magnetics works despite shock, radiation or noise interferences

  9. Pemodelan Markov Switching Autoregressive

    OpenAIRE

    Ariyani, Fiqria Devi; Warsito, Budi; Yasin, Hasbi

    2014-01-01

    Transition from depreciation to appreciation of exchange rate is one of regime switching that ignored by classic time series model, such as ARIMA, ARCH, or GARCH. Therefore, economic variables are modeled by Markov Switching Autoregressive (MSAR) which consider the regime switching. MLE is not applicable to parameters estimation because regime is an unobservable variable. So that filtering and smoothing process are applied to see the regime probabilities of observation. Using this model, tran...

  10. Toward Understanding Phage:Host Interactions in the Rumen; Complete Genome Sequences of Lytic Phages Infecting Rumen Bacteria

    Directory of Open Access Journals (Sweden)

    Rosalind A. Gilbert

    2017-12-01

    Full Text Available The rumen is known to harbor dense populations of bacteriophages (phages predicted to be capable of infecting a diverse range of rumen bacteria. While bacterial genome sequencing projects are revealing the presence of phages which can integrate their DNA into the genome of their host to form stable, lysogenic associations, little is known of the genetics of phages which utilize lytic replication. These phages infect and replicate within the host, culminating in host lysis, and the release of progeny phage particles. While lytic phages for rumen bacteria have been previously isolated, their genomes have remained largely uncharacterized. Here we report the first complete genome sequences of lytic phage isolates specifically infecting three genera of rumen bacteria: Bacteroides, Ruminococcus, and Streptococcus. All phages were classified within the viral order Caudovirales and include two phage morphotypes, representative of the Siphoviridae and Podoviridae families. The phage genomes displayed modular organization and conserved viral genes were identified which enabled further classification and determination of closest phage relatives. Co-examination of bacterial host genomes led to the identification of several genes responsible for modulating phage:host interactions, including CRISPR/Cas elements and restriction-modification phage defense systems. These findings provide new genetic information and insights into how lytic phages may interact with bacteria of the rumen microbiome.

  11. In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus.

    Science.gov (United States)

    Daikoku, Tohru; Kudoh, Ayumi; Fujita, Masatoshi; Sugaya, Yutaka; Isomura, Hiroki; Tsurumi, Tatsuya

    2004-12-24

    The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for maintenance of the viral genome DNA during the latent phase of EBV replication but continues to be synthesized after the induction of viral productive replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that EBNA1 constantly binds to oriP of the EBV genome during not only latent but also lytic infection. Although the total levels of EBNA1 proved constant throughout the latter, the levels of the oriP-bound form were increased as lytic infection proceeded. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments, where viral replication proteins are clustered. Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed broadly in nuclei as fine punctate dots during the latent phase of infection, the protein became redistributed to the viral replication compartments and localized as distinct spots within and/or nearby the compartments after the induction of lytic replication. Taking these findings into consideration, oriP regions of the EBV genome might be organized by EBNA1 into replication domains that may set up scaffolding for lytic replication and transcription.

  12. Probing the structure of glucan lyases – the lytic members of GH31 - by sequence analysis, circular dichroism and proteolysis

    DEFF Research Database (Denmark)

    Ernst, Heidi; Lo Leggio, Leila; Yu, Shukun

    2005-01-01

    Glucan lyase (GL) is a polysaccharide lyase with unique characteristics. It is involved in an alternative pathway for the degradation of alpha-glucans, the anhydrofructose pathway. Sequence similarity suggests that this lytic enzyme belongs to glycoside hydrolase family 31, for which until very r...

  13. Gene Expression of Lytic Endopeptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonads.

    Science.gov (United States)

    Tsfasman, Irina M; Lapteva, Yulia S; Krasovskaya, Ludmila A; Kudryakova, Irina V; Vasilyeva, Natalia V; Granovsky, Igor E; Stepnaya, Olga A

    2015-01-01

    Development of an efficient expression system for (especially secreted) bacterial lytic enzymes is a complicated task due to the specificity of their action. The substrate for such enzymes is peptidoglycan, the main structural component of bacterial cell walls. For this reason, expression of recombinant lytic proteins is often accompanied with lysis of the producing bacterium. This paper presents data on the construction of an inducible system for expression of the lytic peptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonas fluorescens Q2-87, which provides for the successful secretion of these proteins into the culture liquid. In this system, the endopeptidase gene under control of the T7lac promoter was integrated into the bacterial chromosome, as well as the Escherichia coli lactose operon repressor protein gene. The T7 pol gene under lac promoter control, which encodes the phage T7 RNA polymerase, is maintained in Pseudomonas cells on the plasmids. Media and cultivation conditions for the recombinant strains were selected to enable the production of AlpA and AlpB by a simple purification protocol. Production of recombinant lytic enzymes should contribute to the development of new-generation antimicrobial drugs whose application will not be accompanied by selection of resistant microorganisms. © 2015 S. Karger AG, Basel.

  14. Epiphyseal involvement in Erdheim-Chester disease: radiographic and scintigraphic findings in a case with lytic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Hernandez, G.; Tajahuerce-Romera, G.M.; Latorre-Ibanez, M.D.; Lara-Pomares, A. [Servicio de Medicina Nuclear, Hospital Provincial de Castellon (Spain); Vila-Fayos, V. [Servicio de Reumatologia, Hospital Comarcal de Vinaroz (Spain)

    2000-08-01

    We reported a symmetric increase of activity in lower links secondary to Erdheim-Chester disease and demonstrated by bone scans and radiographs. An inusual scintigraphic and radiographic appearance with epiphyseal involvement and lytic lesions is described. Differential diagnosis of bone scan and radiographic findings is discussed. (orig.)

  15. Oxidative cleavage and hydrolytic boosting of cellulose in soybean spent flakes by Trichoderma reesei Cel61A lytic polysaccharide monooxygenase

    DEFF Research Database (Denmark)

    Pierce, Brian; Wittrup Agger, Jane; Wichmann, Jesper

    2017-01-01

    The auxiliary activity family 9 (AA9) copper-dependent lytic polysaccharide monooxygenase (LPMO) from Trichoderma reesei (EG4; TrCel61A) was investigated for its ability to oxidize the complex polysaccharides from soybean. The substrate specificity of the enzyme was assessed against a variety of ...

  16. Lytic Infection of Lactococcus lactis by Bacteriophages Tuc2009 and c2 Triggers Alternative Transcriptional Host Responses

    NARCIS (Netherlands)

    Ainsworth, S.; Zomer, A.L.; Mahony, J.; Sinderen, D. van

    2013-01-01

    Here we present an entire temporal transcriptional profile of Lactococcus lactis subsp. cremoris UC509.9 undergoing lytic infection with two distinct bacteriophages, Tuc2009 and c2. Furthermore, corresponding high-resolution whole-phage genome tiling arrays of both bacteriophages were performed

  17. Needle aspiration biopsy in the diagnosis of lytic bone lesions in histiocytosis X, Ewing's sarcoma and neuroblastoma

    International Nuclear Information System (INIS)

    Thommesen, P.; Frederiksen, P.; Loewhagen, T.; Willems, J.S.

    1978-01-01

    Cytologic smears obtained by needle aspiration biopsy of lytic bone lesions in 15 patients with histiocytosis X, Ewing's sarcoma and neuroblastoma were reviewed. After conventional staining, histiocytosis X could be diagnosed and differentiated from small cell tumours such as Ewing's sarcoma and neuroblastoma. The need for sampling material for cytochemical and ultrastructural analysis of these small cell tumours by needle aspiration is emphasized. (Auth.)

  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. Transient-Switch-Signal Suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1995-01-01

    Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

  20. [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.

  1. Optimal switching using coherent control

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Heuck, Mikkel; Mørk, Jesper

    2013-01-01

    that the switching time, in general, is not limited by the cavity lifetime. Therefore, the total energy required for switching is a more relevant figure of merit than the switching speed, and for a particular two-pulse switching scheme we use calculus of variations to optimize the switching in terms of input energy....

  2. Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.

    Science.gov (United States)

    Zhang, Shilun; Yin, Juan; Zhong, Jiang

    2017-01-01

    Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L -1 ). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

  3. Isolation and life cycle characterization of lytic viruses infecting heterotrophic bacteria and cyanobacteria

    DEFF Research Database (Denmark)

    Middelboe, Mathias; Chan, Amy; Bertelsen, Sif Koldborg

    2010-01-01

    Basic knowledge on viruses infecting heterotrophic bacteria and cyanobacteria is key to future progress in understanding the role of viruses in aquatic systems and the influence of virus–host interactions on microbial mortality, biogeochemical cycles, and genetic exchange. Such studies require......, and discusses the applications and limitations of different isolation procedures. Most work on phage isolation has been carried out with aerobic heterotrophic bacteria and cyanobacteria, culturable both on agar plates and in enriched liquid cultures. The procedures presented here are limited to lytic viruses...... infecting such hosts. In addition to the isolation procedures, methods for life cycle characterization (one-step growth experiments) of bacteriophages and cyanophages are described. Finally, limitations and drawbacks of the proposed methods are assessed and discussed...

  4. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.

    Directory of Open Access Journals (Sweden)

    Marie Samanovic

    2009-01-01

    Full Text Available Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.

  5. 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...

  6. Switched reluctance motor drives

    Indian Academy of Sciences (India)

    Davis RM, Ray WF, Blake RJ 1981 Inverter drive for switched reluctance: circuits and component ratings. Inst. Elec. Eng. Proc. B128: 126-136. Ehsani M. 1991 Position Sensor elimination technique for the switched reluctance motor drive. US Patent No. 5,072,166. Ehsani M, Ramani K R 1993 Direct control strategies based ...

  7. Manually operated coded switch

    International Nuclear Information System (INIS)

    Barnette, J.H.

    1978-01-01

    The disclosure related to a manually operated recodable coded switch in which a code may be inserted, tried and used to actuate a lever controlling an external device. After attempting a code, the switch's code wheels must be returned to their zero positions before another try is made

  8. Switch on, switch off: stiction in nanoelectromechanical switches

    KAUST Repository

    Wagner, Till J W

    2013-06-13

    We present a theoretical investigation of stiction in nanoscale electromechanical contact switches. We develop a mathematical model to describe the deflection of a cantilever beam in response to both electrostatic and van der Waals forces. Particular focus is given to the question of whether adhesive van der Waals forces cause the cantilever to remain in the \\'ON\\' state even when the electrostatic forces are removed. In contrast to previous studies, our theory accounts for deflections with large slopes (i.e. geometrically nonlinear). We solve the resulting equations numerically to study how a cantilever beam adheres to a rigid electrode: transitions between \\'free\\', \\'pinned\\' and \\'clamped\\' states are shown to be discontinuous and to exhibit significant hysteresis. Our findings are compared to previous results from linearized models and the implications for nanoelectromechanical cantilever switch design are discussed. © 2013 IOP Publishing Ltd.

  9. Avalanche photoconductive switching

    Science.gov (United States)

    Pocha, M. D.; Druce, R. L.; Wilson, M. J.; Hofer, W. W.

    This paper describes work being done at Lawrence Livermore National Laboratory on the avalanche mode of operation of laser triggered photoconductive switches. We have been able to generate pulses with amplitudes of 2 kV to 35 kV and rise times of 300 to 500 ps, and with a switching gain (energy of output electrical pulse vs energy of trigger optical pulse) of 10(exp 3) to over 10(exp 5). Switches with two very different physical configurations and with two different illumination wavelengths (1.06 micrometer, 890 nm) exhibit very similar behavior. The avalanche switching behavior, therefore, appears to be related to the material parameters rather than the optical wavelength or switch geometry. Considerable further work needs to be done to fully characterize and understand this mode of operation.

  10. Avalanche photoconductive switching

    Energy Technology Data Exchange (ETDEWEB)

    Pocha, M.D.; Druce, R.L.; Wilson, M.J.; Hofer, W.W.

    1989-01-01

    This paper describes work being done at Lawrence Livermore National Laboratory on the avalanche mode of operation of laser triggered photoconductive switches. We have been able to generate pulses with amplitudes of 2 kV--35 kV and rise times of 300--500 ps, and with a switching gain (energy of output electrical pulse vs energy of trigger optical pulse) of 10{sup 3} to over 10{sup 5}. Switches with two very different physical configurations and with two different illumination wavelengths (1.06 {mu}m, 890 nm) exhibit very similar behavior. The avalanche switching behavior, therefore, appears to be related to the material parameters rather than the optical wavelength or switch geometry. Considerable further work needs to be done to fully characterize and understand this mode of operation. 3 refs., 6 figs.

  11. Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8+ T Cell Recognition across All Three Phases of the Lytic Cycle

    Science.gov (United States)

    Quinn, Laura L.; Zuo, Jianmin; Abbott, Rachel J. M.; Shannon-Lowe, Claire; Tierney, Rosemary J.; Hislop, Andrew D.; Rowe, Martin

    2014-01-01

    CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes. Here we examined the relative contribution of these genes to modulation of CD8+ T cell recognition of EBV lytic antigens expressed at different phases of the replication cycle in EBV-transformed B-cells (LCLs) which spontaneously reactivate lytic cycle. Selective shRNA-mediated knockdown of BNLF2a expression led to more efficient recognition of immediate-early (IE)- and early (E)-derived epitopes by CD8+ T cells, while knock down of BILF1 increased recognition of epitopes from E and late (L)-expressed antigens. Contrary to what might have been predicted from previous ectopic expression studies in EBV-negative model cell lines, the shRNA-mediated inhibition of BGLF5 expression in LCLs showed only modest, if any, increase in recognition of epitopes expressed in any phase of lytic cycle. These data indicate that whilst BNLF2a interferes with antigen presentation with diminishing efficiency as lytic cycle progresses (IE>E>>L), interference by BILF1 increases with progression through lytic cycle (IEevasion functions are actually relevant in the context of lytic virus replication, and secondly identify lytic-cycle phase-specific effects that provide mechanistic insight into the immunodominance pattern seen for CD8+ T cell responses to EBV lytic antigens. PMID:25144360

  12. 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.

  13. DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA.

    Science.gov (United States)

    Wang'ondu, Ruth; Teal, Stuart; Park, Richard; Heston, Lee; Delecluse, Henri; Miller, George

    2015-01-01

    Epstein Barr virus (EBV), like other oncogenic viruses, modulates the activity of cellular DNA damage responses (DDR) during its life cycle. Our aim was to characterize the role of early lytic proteins and viral lytic DNA replication in activation of DNA damage signaling during the EBV lytic cycle. Our data challenge the prevalent hypothesis that activation of DDR pathways during the EBV lytic cycle occurs solely in response to large amounts of exogenous double stranded DNA products generated during lytic viral DNA replication. In immunofluorescence or immunoblot assays, DDR activation markers, specifically phosphorylated ATM (pATM), H2AX (γH2AX), or 53BP1 (p53BP1), were induced in the presence or absence of viral DNA amplification or replication compartments during the EBV lytic cycle. In assays with an ATM inhibitor and DNA damaging reagents in Burkitt lymphoma cell lines, γH2AX induction was necessary for optimal expression of early EBV genes, but not sufficient for lytic reactivation. Studies in lytically reactivated EBV-positive cells in which early EBV proteins, BGLF4, BGLF5, or BALF2, were not expressed showed that these proteins were not necessary for DDR activation during the EBV lytic cycle. Expression of ZEBRA, a viral protein that is necessary for EBV entry into the lytic phase, induced pATM foci and γH2AX independent of other EBV gene products. ZEBRA mutants deficient in DNA binding, Z(R183E) and Z(S186E), did not induce foci of pATM. ZEBRA co-localized with HP1β, a heterochromatin associated protein involved in DNA damage signaling. We propose a model of DDR activation during the EBV lytic cycle in which ZEBRA induces ATM kinase phosphorylation, in a DNA binding dependent manner, to modulate gene expression. ATM and H2AX phosphorylation induced prior to EBV replication may be critical for creating a microenvironment of viral and cellular gene expression that enables lytic cycle progression.

  14. Testing protozoacidal activity of ligand-lytic peptides against termite gut protozoa in vitro (protozoa culture) and in vivo (microinjection into termite hindgut).

    Science.gov (United States)

    Husseneder, Claudia; Sethi, Amit; Foil, Lane; Delatte, Jennifer

    2010-12-29

    We are developing a novel approach to subterranean termite control that would lead to reduced reliance on the use of chemical pesticides. Subterranean termites are dependent on protozoa in the hindguts of workers to efficiently digest wood. Lytic peptides have been shown to kill a variety of protozoan parasites (Mutwiri et al. 2000) and also protozoa in the gut of the Formosan subterranean termite, Coptotermes formosanus (Husseneder and Collier 2009). Lytic peptides are part of the nonspecific immune system of eukaryotes, and destroy the membranes of microorganisms (Leuschner and Hansel 2004). Most lytic peptides are not likely to harm higher eukaryotes, because they do not affect the electrically neutral cholesterol-containing cell membranes of higher eukaryotes (Javadpour et al. 1996). Lytic peptide action can be targeted to specific cell types by the addition of a ligand. For example, Hansel et al. (2007) reported that lytic peptides conjugated with cancer cell membrane receptor ligands could be used to destroy breast cancer cells, while lytic peptides alone or conjugated with non-specific peptides were not effective. Lytic peptides also have been conjugated to human hormones that bind to receptors on tumor cells for targeted destruction of prostate and testicular cancer cells (Leuschner and Hansel 2004). In this article we present techniques used to demonstrate the protozoacidal activity of a lytic peptide (Hecate) coupled to a heptapeptide ligand that binds to the surface membrane of protozoa from the gut of the Formosan subterranean termite. These techniques include extirpation of the gut from termite workers, anaerobic culture of gut protozoa (Pseudotrichonympha grassii, Holomastigotoides hartmanni,Spirotrichonympha leidyi), microscopic confirmation that the ligand marked with a fluorescent dye binds to the termite gut protozoa and other free-living protozoa but not to bacteria or gut tissue. We also demonstrate that the same ligand coupled to a lytic

  15. Energy losses in switches

    International Nuclear Information System (INIS)

    Martin, T.H.; Seamen, J.F.; Jobe, D.O.

    1993-01-01

    The authors experiments show energy losses between 2 and 10 times that of the resistive time predictions. The experiments used hydrogen, helium, air, nitrogen, SF 6 polyethylene, and water for the switching dielectric. Previously underestimated switch losses have caused over predicting the accelerator outputs. Accurate estimation of these losses is now necessary for new high-efficiency pulsed power devices where the switching losses constitute the major portion of the total energy loss. They found that the switch energy losses scale as (V peak I peak ) 1.1846 . When using this scaling, the energy losses in any of the tested dielectrics are almost the same. This relationship is valid for several orders of magnitude and suggested a theoretical basis for these results. Currents up to .65 MA, with voltages to 3 MV were applied to various gaps during these experiments. The authors data and the developed theory indicates that the switch power loss continues for a much longer time than the resistive time, with peak power loss generally occurring at peak current in a ranging discharge instead of the early current time. All of the experiments were circuit code modeled after developing a new switch loss version based on the theory. The circuit code predicts switch energy loss and peak currents as a function of time. During analysis of the data they noticed slight constant offsets between the theory and data that depended on the dielectric. They modified the plasma conductivity for each tested dielectric to lessen this offset

  16. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Daniela F Angelini

    Full Text Available It has long been known that multiple sclerosis (MS is associated with an increased Epstein-Barr virus (EBV seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A and lytic (BZLF-1, BMLF-1 antigens in relapsing-remitting MS patients (n = 113 and healthy donors (HD (n = 43 and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

  17. Electromechanical magnetization switching

    Energy Technology Data Exchange (ETDEWEB)

    Chudnovsky, Eugene M. [Department of Physics and Astronomy, Lehman College and Graduate School, The City University of New York, 250 Bedford Park Boulevard West, Bronx, New York 10468-1589 (United States); Jaafar, Reem [Department of Mathematics, Engineering and Computer Science, LaGuardia Community College, The City University of New York, 31-10 Thomson Avenue, Long Island City, New York 11101 (United States)

    2015-03-14

    We show that the magnetization of a torsional oscillator that, in addition to the magnetic moment also possesses an electrical polarization, can be switched by the electric field that ignites mechanical oscillations at the frequency comparable to the frequency of the ferromagnetic resonance. The 180° switching arises from the spin-rotation coupling and is not prohibited by the different symmetry of the magnetic moment and the electric field as in the case of a stationary magnet. Analytical equations describing the system have been derived and investigated numerically. Phase diagrams showing the range of parameters required for the switching have been obtained.

  18. Electromechanical magnetization switching

    International Nuclear Information System (INIS)

    Chudnovsky, Eugene M.; Jaafar, Reem

    2015-01-01

    We show that the magnetization of a torsional oscillator that, in addition to the magnetic moment also possesses an electrical polarization, can be switched by the electric field that ignites mechanical oscillations at the frequency comparable to the frequency of the ferromagnetic resonance. The 180° switching arises from the spin-rotation coupling and is not prohibited by the different symmetry of the magnetic moment and the electric field as in the case of a stationary magnet. Analytical equations describing the system have been derived and investigated numerically. Phase diagrams showing the range of parameters required for the switching have been obtained

  19. JUNOS Enterprise Switching

    CERN Document Server

    Reynolds, Harry

    2009-01-01

    JUNOS Enterprise Switching is the only detailed technical book on Juniper Networks' new Ethernet-switching EX product platform. With this book, you'll learn all about the hardware and ASIC design prowess of the EX platform, as well as the JUNOS Software that powers it. Not only is this extremely practical book a useful, hands-on manual to the EX platform, it also makes an excellent study guide for certification exams in the JNTCP enterprise tracks. The authors have based JUNOS Enterprise Switching on their own Juniper training practices and programs, as well as the configuration, maintenanc

  20. Switch mode power supply

    International Nuclear Information System (INIS)

    Kim, Hui Jun

    1993-06-01

    This book concentrates on switch mode power supply. It has four parts, which are introduction of switch mode power supply with DC-DC converter such as Buck converter boost converter, Buck-boost converter and PWM control circuit, explanation for SMPS with DC-DC converter modeling and power mode control, resonance converter like resonance switch, converter, multi resonance converter and series resonance and parallel resonance converters, basic test of SMPS with PWM control circuit, Buck converter, Boost converter, flyback converter, forward converter and IC for control circuit.

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. A rapid quantitative activity assay shows that the Vibrio cholerae colonization factor GbpA is an active lytic polysaccharide monooxygenase

    NARCIS (Netherlands)

    Loose, Jennifer S. M.; Forsberg, Zarah; Fraaije, Marco W.; Eijsink, Vincent G. H.; Vaaje-Kolstad, Gustav

    2014-01-01

    The discovery of the copper-dependent lytic polysaccharide monooxygenases (LPMOs) has revealed new territory for chemical and biochemical analysis. These unique mononuclear copper enzymes are abundant, suggesting functional diversity beyond their established roles in the depolymerization of biomass

  12. Unliganded and substrate bound structures of the cellooligosaccharide active lytic polysaccharide monooxygenase LsAA9A at low pH

    DEFF Research Database (Denmark)

    Frandsen, Kristian Erik Høpfner; Poulsen, Jens-Christian Navarro; Tandrup, Tobias

    2017-01-01

    Lytic polysaccharide monooxygenases (LPMOs) have been found to be key components in microbial (bacterial and fungal) degradation of biomass. They are copper metalloenzymes that degrade polysaccharides oxidatively and act in synergy with glycoside hydrolases. Recently crystallographic studies...

  13. 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

  14. 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...

  15. 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...

  16. Utility of lytic bacteriophage in the treatment of multidrug-resistant Pseudomonas aeruginosa septicemia in mice

    Directory of Open Access Journals (Sweden)

    Vinodkumar C

    2008-07-01

    Full Text Available Drug resistance is the major cause of increase in morbidity and mortality in neonates. One thousand six hundred forty-seven suspected septicemic neonates were subjected for microbiological analysis over a period of 5 years. Forty-two P. aeruginosa were isolated and the antibiogram revealed that 28 P. aeruginosa were resistant to almost all the common drugs used (multidrug-resistant. The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. As a result, a novel and most effective approaches for treating infection caused by multidrug-resistant bacteria are urgently required. In this context, one intriguing approach is to use bacteriophages (viruses that kill bacteria in the treatment of infection caused by drug-resistant bacteria. In the present study, the utility of lytic bacteriophages to rescue septicemic mice with multidrug-resistant (MDR P. aeruginosa infection was evaluated. MDR P. aeruginosa was used to induce septicemia in mice by intraperitoneal (i.p. injection of 10 7 CFU. The resulting bacteremia was fatal within 48 hrs. The phage strain used in this study had lytic activity against a wide range of clinical isolates of MDR P. aeruginosa. A single i.p. injection of 3 x 10 9 PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue septicemic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of septicemic mice could be affected only by phage strains able to grow in vitro on the bacterial host used to infect the animals and when such strains are heat-inactivated, they lose their ability to rescue the infected mice. Multidrug-resistant bacteria have

  17. Isolation and characterization of ZZ1, a novel lytic phage that infects Acinetobacter baumannii clinical isolates

    Directory of Open Access Journals (Sweden)

    Jin Jing

    2012-07-01

    Full Text Available Abstract Background Acinetobacter baumannii, a significant nosocomial pathogen, has evolved resistance to almost all conventional antimicrobial drugs. Bacteriophage therapy is a potential alternative treatment for multidrug-resistant bacterial infections. In this study, one lytic bacteriophage, ZZ1, which infects A. baumannii and has a broad host range, was selected for characterization. Results Phage ZZ1 and 3 of its natural hosts, A. baumanni clinical isolates AB09V, AB0902, and AB0901, are described in this study. The 3 strains have different sensitivities to ZZ1, but they have the same sensitivity to antibiotics. They are resistant to almost all of the antibiotics tested, except for polymyxin. Several aspects of the life cycle of ZZ1 were investigated using the sensitive strain AB09V under optimal growth conditions. ZZ1 is highly infectious with a short latent period (9 min and a large burst size (200 PFU/cell. It exhibited the most powerful antibacterial activity at temperatures ranging from 35°C to 39°C. Moreover, when ZZ1 alone was incubated at different pHs and different temperatures, the phage was stable over a wide pH range (4 to 9 and at extreme temperatures (between 50°C and 60°C. ZZ1 possesses a 100-nm icosahedral head containing double-stranded DNA with a total length of 166,682 bp and a 120-nm long contractile tail. Morphologically, it could be classified as a member of the Myoviridae family and the Caudovirales order. Bioinformatic analysis of the phage whole genome sequence further suggested that ZZ1 was more likely to be a new member of the Myoviridae phages. Most of the predicted ORFs of the phage were similar to the predicted ORFs from other Acinetobacter phages. Conclusion The phage ZZ1 has a relatively broad lytic spectrum, high pH stability, strong heat resistance, and efficient antibacterial potential at body temperature. These characteristics greatly increase the utility of this phage as an antibacterial agent

  18. Isolation and characterization of ZZ1, a novel lytic phage that infects Acinetobacter baumannii clinical isolates.

    Science.gov (United States)

    Jin, Jing; Li, Zhen-Jiang; Wang, Shu-Wei; Wang, Shan-Mei; Huang, De-Hai; Li, Ya-Hui; Ma, Yun-Yun; Wang, Jin; Liu, Fang; Chen, Xiang-Dong; Li, Guang-Xing; Wang, Xiao-Ting; Wang, Zhong-Quan; Zhao, Guo-Qiang

    2012-07-28

    Acinetobacter baumannii, a significant nosocomial pathogen, has evolved resistance to almost all conventional antimicrobial drugs. Bacteriophage therapy is a potential alternative treatment for multidrug-resistant bacterial infections. In this study, one lytic bacteriophage, ZZ1, which infects A. baumannii and has a broad host range, was selected for characterization. Phage ZZ1 and 3 of its natural hosts, A. baumanni clinical isolates AB09V, AB0902, and AB0901, are described in this study. The 3 strains have different sensitivities to ZZ1, but they have the same sensitivity to antibiotics. They are resistant to almost all of the antibiotics tested, except for polymyxin. Several aspects of the life cycle of ZZ1 were investigated using the sensitive strain AB09V under optimal growth conditions. ZZ1 is highly infectious with a short latent period (9 min) and a large burst size (200 PFU/cell). It exhibited the most powerful antibacterial activity at temperatures ranging from 35°C to 39°C. Moreover, when ZZ1 alone was incubated at different pHs and different temperatures, the phage was stable over a wide pH range (4 to 9) and at extreme temperatures (between 50°C and 60°C). ZZ1 possesses a 100-nm icosahedral head containing double-stranded DNA with a total length of 166,682 bp and a 120-nm long contractile tail. Morphologically, it could be classified as a member of the Myoviridae family and the Caudovirales order. Bioinformatic analysis of the phage whole genome sequence further suggested that ZZ1 was more likely to be a new member of the Myoviridae phages. Most of the predicted ORFs of the phage were similar to the predicted ORFs from other Acinetobacter phages. The phage ZZ1 has a relatively broad lytic spectrum, high pH stability, strong heat resistance, and efficient antibacterial potential at body temperature. These characteristics greatly increase the utility of this phage as an antibacterial agent; thus, it should be further investigated.

  19. A comparative study on the activity of fungal lytic polysaccharide monooxygenases for the depolymerization of cellulose in soybean spent flakes

    DEFF Research Database (Denmark)

    Pierce, Brian; Wittrup Agger, Jane; Zhang, Zhenghong

    2017-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes capable of the oxidative breakdown of polysaccharides. They are of industrial interest due to their ability to enhance the enzymatic depolymerization of recalcitrant substrates by glycoside hydrolases. In this paper, twenty......-four lytic polysaccharide monooxygenases (LPMOs) expressed in Trichoderma reesei were evaluated for their ability to oxidize the complex polysaccharides in soybean spent flakes, an abundant and industrially relevant substrate. TrCel61A, a soy-polysaccharide-active AA9 LPMO from T. reesei, was used...... as a benchmark in this evaluation. In total, seven LPMOs demonstrated activity on pretreated soy spent flakes, with the products from enzymatic treatments evaluated using mass spectrometry and high performance anion exchange chromatography. The hydrolytic boosting effect of the top-performing enzymes...

  20. Optical switching systems using nanostructures

    DEFF Research Database (Denmark)

    Stubkjær, Kristian

    2004-01-01

    High capacity multiservice optical networks require compact and efficient switches. The potential benefits of optical switch elements based on nanostructured material are reviewed considering various material systems.......High capacity multiservice optical networks require compact and efficient switches. The potential benefits of optical switch elements based on nanostructured material are reviewed considering various material systems....

  1. Lytic bacteriophages reduce Escherichia coli O157: H7 on fresh cut lettuce introduced through cross-contamination.

    Science.gov (United States)

    Ferguson, Sean; Roberts, Cheryl; Handy, Eric; Sharma, Manan

    2013-01-01

    The role of lytic bacteriophages in preventing cross contamination of produce has not been evaluated. A cocktail of three lytic phages specific for E. coli O157:H7 (EcoShield™) or a control (phosphate buffered saline, PBS) was applied to lettuce by either; (1) immersion of lettuce in 500 ml of EcoShield™ 8.3 log PFU/ml or 9.8 log PFU/ml for up to 2 min before inoculation with E. coli O157:H7; (2) spray-application of EcoShield™ (9.3 log PFU/ml) to lettuce after inoculation with E. coli O157:H7 (4.10 CFU/cm 2 ) following exposure to 50 μg/ml chlorine for 30 sec. After immersion studies, lettuce was spot-inoculated with E. coli O157:H7 (2.38 CFU/cm 2 ). Phage-treated, inoculated lettuce pieces were stored at 4°C for and analyzed for E. coli O157:H7 populations for up to 7 d. Immersion of lettuce in 9.8 log PFU/ml EcoShield™ for 2 min significantly (p PFU/ml) resulted in the deposition of high concentrations (7.8 log log PFU/cm 2 ) of bacteriophages on the surface of fresh cut lettuce, potentially contributing to the efficacy of the lytic phages on lettuce. Spraying phages on to inoculated fresh cut lettuce after being washed in hypochlorite solution was significantly more effective in reducing E. coli O157:H7 populations (2.22 log CFU/cm 2 ) on day 0 compared with control treatments (4.10 log CFU/cm 2 ). Both immersion and spray treatments provided protection from E. coli O157:H7 contamination on lettuce, but spray application of lytic bacteriophages to lettuce was more effective in immediately reducing E. coli O157:H7 populations fresh cut lettuce.

  2. AtlA Functions as a Peptidoglycan Lytic Transglycosylase in the Neisseria gonorrhoeae Type IV Secretion System▿

    OpenAIRE

    Kohler, Petra L.; Hamilton, Holly L.; Cloud-Hansen, Karen; Dillard, Joseph P.

    2007-01-01

    Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We chara...

  3. Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii*

    OpenAIRE

    Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

    2015-01-01

    Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure ...

  4. Primary intraosseous atypical inflammatory meningioma presenting as a lytic skull lesion: Case report with review of literature.

    Science.gov (United States)

    Bohara, Sangita; Agarwal, Swapnil; Khurana, Nita; Pandey, P N

    2016-01-01

    Primary extradural meningiomas of the skull comprise 1% of all meningiomas, and lytic skull meningiomas are still rarer and are said to be more aggressive. We present a case of 38-year-old male with an extradural tumor which on histopathological examination showed features of inflammatory atypical meningioma (WHO Grade II). The intense inflammatory nature of osteolytic primary intraosseous meningioma has not been reported before. This entity deserves special mention because of the need for adjuvant therapy and proper follow-up.

  5. 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

  6. Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

    Directory of Open Access Journals (Sweden)

    Anna Kabanova

    2016-04-01

    Full Text Available Suppression of the cytotoxic T cell (CTL immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs, but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL. Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8. We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Crystal Structures of the SpoIID Lytic Transglycosylases Essential for Bacterial Sporulation.

    Science.gov (United States)

    Nocadello, Salvatore; Minasov, George; Shuvalova, Ludmilla S; Dubrovska, Ievgeniia; Sabini, Elisabetta; Anderson, Wayne F

    2016-07-15

    Bacterial spores are the most resistant form of life known on Earth and represent a serious problem for (i) bioterrorism attack, (ii) horizontal transmission of microbial pathogens in the community, and (iii) persistence in patients and in a nosocomial environment. Stage II sporulation protein D (SpoIID) is a lytic transglycosylase (LT) essential for sporulation. The LT superfamily is a potential drug target because it is active in essential bacterial processes involving the peptidoglycan, which is unique to bacteria. However, the absence of structural information for the sporulation-specific LT enzymes has hindered mechanistic understanding of SpoIID. Here, we report the first crystal structures with and without ligands of the SpoIID family from two community relevant spore-forming pathogens, Bacillus anthracis and Clostridium difficile. The structures allow us to visualize the overall architecture, characterize the substrate recognition model, identify critical residues, and provide the structural basis for catalysis by this new family of enzymes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Determination of lytic enzyme activities of indigenous Trichoderma isolates from Pakistan.

    Science.gov (United States)

    Asad, Saeed Ahmad; Tabassum, Ayesha; Hameed, Abdul; Hassan, Fayyaz Ul; Afzal, Aftab; Khan, Sabaz Ali; Ahmed, Rafiq; Shahzad, Muhammad

    2015-01-01

    This study investigated lytic enzyme activities in three indigenous Trichoderma strains namely, Trichoderma asperellum, Trichoderma harzianum and Trichoderma sp. Native Trichoderma strains and a virulent strain of Rhizoctonia solani isolated from infected bean plants were also included in the study. Enzyme activities were determined by measuring sugar reduction by dinitrosalicylic acid (DNS) method using suitable substrates. The antagonists were cultured in minimal salt medium with the following modifications: medium A (1 g of glucose), medium B (0.5 g of glucose + 0.5 g of deactivated R. solani mycelia), medium C (1.0 g of deactivated respective antagonist mycelium) and medium D (1 g of deactivated R. solani mycelia). T asperellum showed presence of higher amounts of chitinases, β-1, 3-glucanases and xylanases in extracellular protein extracts from medium D as compared to medium A. While, the higher activities of glucosidases and endoglucanses were shown in medium D extracts by T. harzianum. β-glucosidase activities were lower compared with other enzymes; however, activities of the extracts of medium D were significantly different. T. asperellum exhibited maximum inhibition (97.7%). On the other hand, Trichoderma sp. did not show any effect on mycelia growth of R. solani on crude extract.

  15. Lytic phages obscure the cost of antibiotic resistance in Escherichia coli.

    Science.gov (United States)

    Tazzyman, Samuel J; Hall, Alex R

    2015-03-17

    The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods.

  16. Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules.

    Science.gov (United States)

    Elemam, Noha Mousaad; Hannawi, Suad; Maghazachi, Azzam A

    2017-12-10

    Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce T H 2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

  17. Innate Lymphoid Cells (ILCs as Mediators of Inflammation, Release of Cytokines and Lytic Molecules

    Directory of Open Access Journals (Sweden)

    Noha Mousaad Elemam

    2017-12-01

    Full Text Available Innate lymphoid cells (ILCs are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

  18. Determination of lytic enzyme activities of indigenous Trichoderma isolates from Pakistan

    Science.gov (United States)

    Asad, Saeed Ahmad; Tabassum, Ayesha; Hameed, Abdul; Hassan, Fayyaz ul; Afzal, Aftab; Khan, Sabaz Ali; Ahmed, Rafiq; Shahzad, Muhammad

    2015-01-01

    Abstract This study investigated lytic enzyme activities in three indigenous Trichoderma strains namely, Trichoderma asperellum, Trichoderma harzianum and Trichoderma sp. Native Trichoderma strains and a virulent strain of Rhizoctonia solani isolated from infected bean plants were also included in the study. Enzyme activities were determined by measuring sugar reduction by dinitrosalicylic acid (DNS) method using suitable substrates. The antagonists were cultured in minimal salt medium with the following modifications: medium A (1 g of glucose), medium B (0.5 g of glucose + 0.5 g of deactivated R. solani mycelia), medium C (1.0 g of deactivated respective antagonist mycelium) and medium D (1 g of deactivated R. solani mycelia). T asperellum showed presence of higher amounts of chitinases, β-1, 3-glucanases and xylanases in extracellular protein extracts from medium D as compared to medium A. While, the higher activities of glucosidases and endoglucanses were shown in medium D extracts by T. harzianum. β-glucosidase activities were lower compared with other enzymes; however, activities of the extracts of medium D were significantly different. T. asperellum exhibited maximum inhibition (97.7%). On the other hand, Trichoderma sp. did not show any effect on mycelia growth of R. solani on crude extract. PMID:26691463

  19. Differential impact of lytic viruses on prokaryotic morphopopulations in a tropical estuarine system (Cochin estuary, India).

    Science.gov (United States)

    Jasna, Vijayan; Pradeep Ram, Angia Sriram; Parvathi, Ammini; Sime-Ngando, Telesphore

    2018-01-01

    Our understanding on the importance of viral lysis in the functioning of tropical estuarine ecosystem is limited. This study examines viral infection of prokaryotes and subsequent lysis of cells belonging to different morphotypes across a salinity gradient in monsoon driven estuarine ecosystem (Cochin estuary, India). High standing stock of viruses and prokaryotes accompanied by lytic infection rates in the euryhaline/mesohaline region of the estuary suggests salinity to have an influential role in driving interactions between prokaryotes and viruses. High prokaryotic mortality rates, up to 42% of prokaryote population in the pre-monsoon season is further substantiated by a high virus to prokaryote ratio (VPR), suggesting that maintenance of a high number of viruses is dependent on the most active fraction of bacterioplankton. Although myoviruses were the dominant viral morphotype (mean = 43%) throughout the study period, there was significant variation among prokaryotic morphotypes susceptible to viral infection. Among them, the viral infected short rod prokaryote morphotype with lower burst estimates (mean = 18 viruses prokaryote-1) was dominant (35%) in the dry seasons whereas a substantial increase in cocci forms (30%) infected by viruses with high burst size (mean = 31 viruses prokaryote-1) was evident during the monsoon season. Such preferential infections of prokaryotic morphopopulations with respect to seasons can have a strong and variable impact on the carbon and energy flow in this tropical ecosystem.

  20. The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.

    Science.gov (United States)

    Crépin, Sébastien; Ottosen, Elizabeth N; Peters, Katharina; Smith, Sara N; Himpsl, Stephanie D; Vollmer, Waldemar; Mobley, Harry L T

    2018-06-08

    Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  1. Characterisation and genome sequence of the lytic Acinetobacter baumannii bacteriophage vB_AbaS_Loki.

    Directory of Open Access Journals (Sweden)

    Dann Turner

    Full Text Available Acinetobacter baumannii has emerged as an important nosocomial pathogen in healthcare and community settings. While over 100 of Acinetobacter phages have been described in the literature, relatively few have been sequenced. This work describes the characterisation and genome annotation of a new lytic Acinetobacter siphovirus, vB_AbaS_Loki, isolated from activated sewage sludge. Sequencing revealed that Loki encapsulates a 41,308 bp genome, encoding 51 predicted open reading frames. Loki is most closely related to Acinetobacter phage IME_AB3 and more distantly related to Burkholderia phage KL1, Paracoccus phage vB_PmaS_IMEP1 and Pseudomonas phages vB_Pae_Kakheti25, vB_PaeS_SCH_Ab26 and PA73. Loki is characterised by a narrow host range, among the 40 Acinetobacter isolates tested, productive infection was only observed for the propagating host, A. baumannii ATCC 17978. Plaque formation was found to be dependent upon the presence of Ca2+ ions and adsorption to host cells was abolished upon incubation with a mutant of ATCC 17978 encoding a premature stop codon in lpxA. The complete genome sequence of vB_AbaS_Loki was deposited in the European Nucleotide Archive (ENA under the accession number LN890663.

  2. 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).

  3. Energy reversible switching from amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.; Smith, Casey; Hussain, Muhammad Mustafa

    2013-01-01

    We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young's modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young's modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

  4. Energy reversible switching from amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-08-01

    We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young\\'s modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young\\'s modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. 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.

  10. 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...

  11. 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).

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

    DEFF Research Database (Denmark)

    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...

  13. 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...

  14. 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...

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Optical computer switching network

    Science.gov (United States)

    Clymer, B.; Collins, S. A., Jr.

    1985-01-01

    The design for an optical switching system for minicomputers that uses an optical spatial light modulator such as a Hughes liquid crystal light valve is presented. The switching system is designed to connect 80 minicomputers coupled to the switching system by optical fibers. The system has two major parts: the connection system that connects the data lines by which the computers communicate via a two-dimensional optical matrix array and the control system that controls which computers are connected. The basic system, the matrix-based connecting system, and some of the optical components to be used are described. Finally, the details of the control system are given and illustrated with a discussion of timing.

  20. Stochastic Switching Dynamics

    DEFF Research Database (Denmark)

    Simonsen, Maria

    This thesis treats stochastic systems with switching dynamics. Models with these characteristics are studied from several perspectives. Initially in a simple framework given in the form of stochastic differential equations and, later, in an extended form which fits into the framework of sliding...... mode control. It is investigated how to understand and interpret solutions to models of switched systems, which are exposed to discontinuous dynamics and uncertainties (primarily) in the form of white noise. The goal is to gain knowledge about the performance of the system by interpreting the solution...

  1. 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.

  2. Identification of the Receptor-Binding Protein in Lytic Leuconostoc pseudomesenteroides Bacteriophages

    DEFF Research Database (Denmark)

    Kot, Witold Piotr; Hammer, Karin; Neve, Horst

    2013-01-01

    Two phages, P793 and ΦLN04, sharing 80.1% nucleotide sequence identity but having different strains of Leuconostoc pseudomesenteroides as hosts, were selected for identification of the host determinant gene. Construction of chimeric phages leading to the expected switch in host range identified t...

  3. Very high plasma switches. Basic plasma physics and switch technology

    International Nuclear Information System (INIS)

    Doucet, H.J.; Roche, M.; Buzzi, J.M.

    1988-01-01

    A review of some high power switches recently developed for very high power technology is made with a special attention to the aspects of plasma physics involved in the mechanisms, which determine the limits of the possible switching parameters

  4. 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

  5. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

    Science.gov (United States)

    Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

    2018-01-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

  6. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Science.gov (United States)

    Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

    2017-02-01

    Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  7. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Directory of Open Access Journals (Sweden)

    Nidhi Jain

    2017-02-01

    Full Text Available Following Japanese encephalitis virus (JEV infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null are highly susceptible and die over 10-18 day period as compared to the wild-type (WT mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB. Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  8. Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells

    Science.gov (United States)

    2011-01-01

    Background Several naturally occurring cationic antimicrobial peptides (CAPs), including bovine lactoferricin (LfcinB), display promising anticancer activities. These peptides are unaffected by multidrug resistance mechanisms and have been shown to induce a protective immune response against solid tumors, thus making them interesting candidates for developing novel lead structures for anticancer treatment. Recently, we showed that the anticancer activity by LfcinB was inhibited by the presence of heparan sulfate (HS) on the surface of tumor cells. Based on extensive structure-activity relationship studies performed on LfcinB, shorter and more potent peptides have been constructed. In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS) on their cytotoxic activity. Methods Various cell lines and red blood cells were used to investigate the anticancer activity and selectivity of the peptides. The cytotoxic effect of the peptides against the different cell lines was measured by use of a colorimetric MTT viability assay. The influence of HS and CS on their cytotoxic activity was evaluated by using HS/CS expressing and HS/CS deficient cell lines. The ability of soluble HS and CS to inhibit the cytotoxic activity of the peptides and the peptides' affinity for HS and CS were also investigated. Results The 9-mer peptides displayed selective anticancer activity. Cells expressing HS/CS were equally or more susceptible to the peptides than cells not expressing HS/CS. The peptides displayed a higher affinity for HS compared to CS, and exogenously added HS inhibited the cytotoxic effect of the peptides. Conclusions In contrast to the previously reported inhibitory effect of HS on LfcinB, the present study shows that the cytotoxic activity of small lytic peptides was increased or not affected by cell surface HS. PMID:21453492

  9. Using lytic bacteriophages to eliminate or significantly reduce contamination of food by foodborne bacterial pathogens.

    Science.gov (United States)

    Sulakvelidze, Alexander

    2013-10-01

    Bacteriophages (also called 'phages') are viruses that kill bacteria. They are arguably the oldest (3 billion years old, by some estimates) and most ubiquitous (total number estimated to be 10(30) -10(32) ) known organisms on Earth. Phages play a key role in maintaining microbial balance in every ecosystem where bacteria exist, and they are part of the normal microflora of all fresh, unprocessed foods. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention focused on using them to improve food safety. That approach, called 'phage biocontrol', typically includes three main types of applications: (i) using phages to treat domesticated livestock in order to reduce their intestinal colonization with, and shedding of, specific bacterial pathogens; (ii) treatments for decontaminating inanimate surfaces in food-processing facilities and other food establishments, so that foods processed on those surfaces are not cross-contaminated with the targeted pathogens; and (iii) post-harvest treatments involving direct applications of phages onto the harvested foods. This mini-review primarily focuses on the last type of intervention, which has been gaining the most momentum recently. Indeed, the results of recent studies dealing with improving food safety, and several recent regulatory approvals of various commercial phage preparations developed for post-harvest food safety applications, strongly support the idea that lytic phages may provide a safe, environmentally-friendly, and effective approach for significantly reducing contamination of various foods with foodborne bacterial pathogens. However, some important technical and nontechnical problems may need to be addressed before phage biocontrol protocols can become an integral part of routine food safety intervention strategies implemented by food industries in the USA. © 2013 Society of Chemical Industry.

  10. Antibacterial Efficacy of Lytic Bacteriophages against Antibiotic-Resistant Klebsiella Species

    Directory of Open Access Journals (Sweden)

    M. Khajeh Karamoddini

    2011-01-01

    Full Text Available Bacterial resistance to antibiotics is a leading and highly prevalent problem in the treatment of infectious diseases. Bacteriophages (phages appear to be effective and safe alternatives for the treatment of resistant infections because of their specificity for bacterial species and lack of infectivity in eukaryotic cells. The present study aimed to isolate bacteriophages against Klebsiella spp. and evaluate their efficacy against antibiotic-resistant species. Seventy-two antibiotic-resistant Klebsiella spp. were isolated from samples of patients who referred to the Ghaem Hospital (Mashhad, Iran. Lytic bacteriophages against Klebsiella spp. were isolated from wastewater of the septic tank of the same hospital. Bactericidal activity of phages against resistant Klebsiella spp. was tested in both liquid (tube method; after 1 and 24 h of incubation and solid (double-layer agar plate method; after 24 h of incubation phases. In each method, three different concentrations of bacteriophages (low: 107 PFU/mL were used. Bacteriophages showed promising bactericidal activity at all assessed concentrations, regardless of the test method and duration of incubation. Overall, bactericidal effects were augmented at higher concentrations. In the tube method, higher activity was observed after 24 h of incubation compared to the 1-h incubation. The bactericidal effects were also higher in the tube method compared to the double-layer agar plate method after 24 h of incubation. The findings of the present study suggest that bacteriophages possess effective bactericidal activity against resistant Klebsiella spp. These bactericidal activities are influenced by phage concentration, duration of incubation, and test method.

  11. Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells

    Directory of Open Access Journals (Sweden)

    Lindin Inger

    2011-03-01

    Full Text Available Abstract Background Several naturally occurring cationic antimicrobial peptides (CAPs, including bovine lactoferricin (LfcinB, display promising anticancer activities. These peptides are unaffected by multidrug resistance mechanisms and have been shown to induce a protective immune response against solid tumors, thus making them interesting candidates for developing novel lead structures for anticancer treatment. Recently, we showed that the anticancer activity by LfcinB was inhibited by the presence of heparan sulfate (HS on the surface of tumor cells. Based on extensive structure-activity relationship studies performed on LfcinB, shorter and more potent peptides have been constructed. In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS on their cytotoxic activity. Methods Various cell lines and red blood cells were used to investigate the anticancer activity and selectivity of the peptides. The cytotoxic effect of the peptides against the different cell lines was measured by use of a colorimetric MTT viability assay. The influence of HS and CS on their cytotoxic activity was evaluated by using HS/CS expressing and HS/CS deficient cell lines. The ability of soluble HS and CS to inhibit the cytotoxic activity of the peptides and the peptides' affinity for HS and CS were also investigated. Results The 9-mer peptides displayed selective anticancer activity. Cells expressing HS/CS were equally or more susceptible to the peptides than cells not expressing HS/CS. The peptides displayed a higher affinity for HS compared to CS, and exogenously added HS inhibited the cytotoxic effect of the peptides. Conclusions In contrast to the previously reported inhibitory effect of HS on LfcinB, the present study shows that the cytotoxic activity of small lytic peptides was increased or not affected by cell surface HS.

  12. Ultrafast gas switching experiments

    International Nuclear Information System (INIS)

    Frost, C.A.; Martin, T.H.; Patterson, P.E.; Rinehart, L.F.; Rohwein, G.J.; Roose, L.D.; Aurand, J.F.; Buttram, M.T.

    1993-01-01

    We describe recent experiments which studied the physics of ultrafast gas breakdown under the extreme overvoltages which occur when a high pressure gas switch is pulse charged to hundreds of kV in 1 ns or less. The highly overvolted peaking gaps produce powerful electromagnetic pulses with risetimes Khz at > 100 kV/m E field

  13. An integrated circuit switch

    Science.gov (United States)

    Bonin, E. L.

    1969-01-01

    Multi-chip integrated circuit switch consists of a GaAs photon-emitting diode in close proximity with S1 phototransistor. A high current gain is obtained when the transistor has a high forward common-emitter current gain.

  14. The Octopus switch

    NARCIS (Netherlands)

    Havinga, Paul J.M.

    2000-01-01

    This chapter1 discusses the interconnection architecture of the Mobile Digital Companion. The approach to build a low-power handheld multimedia computer presented here is to have autonomous, reconfigurable modules such as network, video and audio devices, interconnected by a switch rather than by a

  15. Untriggered water switching

    International Nuclear Information System (INIS)

    Van Devender, J.P.; Martin, T.H.

    Recent experiments indicate that synchronous untriggered multichannel switching in water will permit the development of relatively simple, ultra-low impedance, short pulse, relativistic electron beam (REB) accelerators. These experiments resulted in the delivery of a 1.5 MV, 0.75 MA, 15 ns pulse into a two-ohm line with a current risetime of 2 x 10 14 A/sec. The apparatus consisted of a 3 MV Marx generator and a series of three 112 cm wide strip water lines separated by two edge-plane water-gap switches. The Marx generator charged the first line in less than 400 ns. The first switch then formed five or more channels. The second line was charged in 60 ns and broke down with 10 to 25 channels at a mean field of 1.6 MV/cm. The closure time of each spark channel along both switches was measured with a streak camera and showed low jitter. The resulting fast pulse line construction is simpler and should provide considerable costs savings from previous designs. Multiples of these low impedance lines in parallel can be employed to obtain power levels in the 10 14 W range for REB fusion studies. (U.S.)

  16. Control synthesis of switched systems

    CERN Document Server

    Zhao, Xudong; Niu, Ben; Wu, Tingting

    2017-01-01

    This book offers its readers a detailed overview of the synthesis of switched systems, with a focus on switching stabilization and intelligent control. The problems investigated are not only previously unsolved theoretically but also of practical importance in many applications: voltage conversion, naval piloting and navigation and robotics, for example. The book considers general switched-system models and provides more efficient design methods to bring together theory and application more closely than was possible using classical methods. It also discusses several different classes of switched systems. For general switched linear systems and switched nonlinear systems comprising unstable subsystems, it introduces novel ideas such as invariant subspace theory and the time-scheduled Lyapunov function method of designing switching signals to stabilize the underlying systems. For some typical switched nonlinear systems affected by various complex dynamics, the book proposes novel design approaches based on inte...

  17. 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

  18. 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

  19. Cooperation between Epstein-Barr virus immune evasion proteins spreads protection from CD8+ T cell recognition across all three phases of the lytic cycle.

    Directory of Open Access Journals (Sweden)

    Laura L Quinn

    2014-08-01

    Full Text Available CD8+ T cell responses to Epstein-Barr virus (EBV lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE and some early (E antigens are more frequently observed than responses to epitopes of late (L expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes. Here we examined the relative contribution of these genes to modulation of CD8+ T cell recognition of EBV lytic antigens expressed at different phases of the replication cycle in EBV-transformed B-cells (LCLs which spontaneously reactivate lytic cycle. Selective shRNA-mediated knockdown of BNLF2a expression led to more efficient recognition of immediate-early (IE- and early (E-derived epitopes by CD8+ T cells, while knock down of BILF1 increased recognition of epitopes from E and late (L-expressed antigens. Contrary to what might have been predicted from previous ectopic expression studies in EBV-negative model cell lines, the shRNA-mediated inhibition of BGLF5 expression in LCLs showed only modest, if any, increase in recognition of epitopes expressed in any phase of lytic cycle. These data indicate that whilst BNLF2a interferes with antigen presentation with diminishing efficiency as lytic cycle progresses (IE>E>>L, interference by BILF1 increases with progression through lytic cycle (IElytic virus replication, and secondly identify lytic-cycle phase-specific effects that provide mechanistic

  20. Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens.

    Directory of Open Access Journals (Sweden)

    Cynthia J Snider

    Full Text Available Plasmodium falciparum malaria (Pf-malaria and Epstein Barr Virus (EBV infections coexist in children at risk for endemic Burkitt's lymphoma (eBL; yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years in Kenya from 2002-2004. Prevalence ratios (PR and 95% confidence intervals (CI were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5-9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30-0.99. Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5-9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.

  1. Cloning and expression analysis of genes encoding lytic endopeptidases L1 and L5 from Lysobacter sp. strain XL1.

    Science.gov (United States)

    Lapteva, Y S; Zolova, O E; Shlyapnikov, M G; Tsfasman, I M; Muranova, T A; Stepnaya, O A; Kulaev, I S; Granovsky, I E

    2012-10-01

    Lytic enzymes are the group of hydrolases that break down structural polymers of the cell walls of various microorganisms. In this work, we determined the nucleotide sequences of the Lysobacter sp. strain XL1 alpA and alpB genes, which code for, respectively, secreted lytic endopeptidases L1 (AlpA) and L5 (AlpB). In silico analysis of their amino acid sequences showed these endopeptidases to be homologous proteins synthesized as precursors similar in structural organization: the mature enzyme sequence is preceded by an N-terminal signal peptide and a pro region. On the basis of phylogenetic analysis, endopeptidases AlpA and AlpB were assigned to the S1E family [clan PA(S)] of serine peptidases. Expression of the alpA and alpB open reading frames (ORFs) in Escherichia coli confirmed that they code for functionally active lytic enzymes. Each ORF was predicted to have the Shine-Dalgarno sequence located at a canonical distance from the start codon and a potential Rho-independent transcription terminator immediately after the stop codon. The alpA and alpB mRNAs were experimentally found to be monocistronic; transcription start points were determined for both mRNAs. The synthesis of the alpA and alpB mRNAs was shown to occur predominantly in the late logarithmic growth phase. The amount of alpA mRNA in cells of Lysobacter sp. strain XL1 was much higher, which correlates with greater production of endopeptidase L1 than of L5.

  2. Unprecedented evidence for high viral abundance and lytic activity in coral reef waters of the South Pacific Ocean

    Directory of Open Access Journals (Sweden)

    Jérôme P. Payet

    2014-09-01

    Full Text Available Despite nutrient-depleted conditions, coral reef waters harbor abundant and diverse microbes; as major agents of microbial mortality, viruses are likely to influence microbial processes in these ecosystems. However, little is known about marine viruses in these rapidly changing ecosystems. Here we examined spatial and short-term temporal variability in marine viral abundance and viral lytic activity across various reef habitats surrounding Moorea Island (French Polynesia in the South Pacific. Water samples were collected along 4 regional cross-reef transects and during a time-series in Opunohu Bay. Results revealed high viral abundance (range: 5.6 x 106 – 3.6 x 107 viruses ml-1 and lytic viral production (range: 1.5 x 109 – 9.2 x 1010 viruses l-1 d-1. Flow cytometry revealed that viral assemblages were composed of three subsets that each displayed distinct spatiotemporal relationships with nutrient concentrations and autotrophic and heterotrophic microbial abundances. The results highlight dynamic shifts in viral community structure and imply that each of these three subsets is ecologically important and likely to infect distinct microbial hosts in reef waters. Based on viral-reduction approach, we estimate that lytic viruses were responsible for the removal of ca. 24% to 367% of bacterial standing stock d-1 and the release of ca. 1.1 to 62 µg of organic carbon l-1 d-1 in reef waters. Overall, this work demonstrates the highly dynamic distribution of viruses and their critical roles in controlling microbial mortality and nutrient cycling in coral reef water ecosystems.

  3. AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

    Science.gov (United States)

    Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

    2007-08-01

    Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

  4. Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii.

    Science.gov (United States)

    Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

    2016-01-01

    Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii*

    Science.gov (United States)

    Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

    2016-01-01

    Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells. PMID:26518878

  6. 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...

  7. Synchronization Between Two Different Switched Chaotic Systems By Switching Control

    Directory of Open Access Journals (Sweden)

    Du Li Ming

    2016-01-01

    Full Text Available This paper is concerned with the synchronization problem of two different switched chaotic systems, considering the general case that the master-slave switched chaotic systems have uncertainties. Two basic problems are considered: one is projective synchronization of switched chaotic systems under arbitrary switching; the other is projective synchronization of switched chaotic systems by design of switching when synchronization cannot achieved by using any subsystems alone. For the two problems, common Lyapunov function method and multiple Lyapunov function method are used respectively, an adaptive control scheme has been presented, some sufficient synchronization conditions are attainted, and the switching signal is designed. Finally, the numerical simulation is provide to show the effectiveness of our method.

  8. Laser activated superconducting switch

    International Nuclear Information System (INIS)

    Wolf, A.A.

    1976-01-01

    A superconducting switch or bistable device is described consisting of a superconductor in a cryogen maintaining a temperature just below the transition temperature, having a window of the proper optical frequency band for passing a laser beam which may impinge on the superconductor when desired. The frequency of the laser is equal to or greater than the optical absorption frequency of the superconducting material and is consistent with the ratio of the gap energy of the switch material to Planck's constant, to cause depairing of electrons, and thereby normalize the superconductor. Some embodiments comprise first and second superconducting metals. Other embodiments feature the two superconducting metals separated by a thin film insulator through which the superconducting electrons tunnel during superconductivity

  9. Optical fiber switch

    Science.gov (United States)

    Early, James W.; Lester, Charles S.

    2002-01-01

    Optical fiber switches operated by electrical activation of at least one laser light modulator through which laser light is directed into at least one polarizer are used for the sequential transport of laser light from a single laser into a plurality of optical fibers. In one embodiment of the invention, laser light from a single excitation laser is sequentially transported to a plurality of optical fibers which in turn transport the laser light to separate individual remotely located laser fuel ignitors. The invention can be operated electro-optically with no need for any mechanical or moving parts, or, alternatively, can be operated electro-mechanically. The invention can be used to switch either pulsed or continuous wave laser light.

  10. Coulomb Blockade Plasmonic Switch.

    Science.gov (United States)

    Xiang, Dao; Wu, Jian; Gordon, Reuven

    2017-04-12

    Tunnel resistance can be modulated with bias via the Coulomb blockade effect, which gives a highly nonlinear response current. Here we investigate the optical response of a metal-insulator-nanoparticle-insulator-metal structure and show switching of a plasmonic gap from insulator to conductor via Coulomb blockade. By introducing a sufficiently large charging energy in the tunnelling gap, the Coulomb blockade allows for a conductor (tunneling) to insulator (capacitor) transition. The tunnelling electrons can be delocalized over the nanocapacitor again when a high energy penalty is added with bias. We demonstrate that this has a huge impact on the plasmonic resonance of a 0.51 nm tunneling gap with ∼70% change in normalized optical loss. Because this structure has a tiny capacitance, there is potential to harness the effect for high-speed switching.

  11. Cryogenic switched MOSFET characterization

    Science.gov (United States)

    1981-01-01

    Both p channel and n channel enhancement mode MOSFETs can be readily switched on and off at temperatures as low as 2.8 K so that switch sampled readout of a VLWIR Ge:Ga focal plane is electronically possible. Noise levels as low as 100 rms electrons per sample (independent of sample rate) can be achieved using existing p channel MOSFETs, at overall rates up to 30,000 samples/second per multiplexed channel (e.g., 32 detectors at a rate of almost 1,000 frames/second). Run of the mill devices, including very low power dissipation n channel FETs would still permit noise levels of the order of 500 electrons/sample.

  12. Practical switching power supply design

    CERN Document Server

    Brown, Martin C

    1990-01-01

    Take the ""black magic"" out of switching power supplies with Practical Switching Power Supply Design! This is a comprehensive ""hands-on"" guide to the theory behind, and design of, PWM and resonant switching supplies. You'll find information on switching supply operation and selecting an appropriate topology for your application. There's extensive coverage of buck, boost, flyback, push-pull, half bridge, and full bridge regulator circuits. Special attention is given to semiconductors used in switching supplies. RFI/EMI reduction, grounding, testing, and safety standards are also deta

  13. Genomic analysis of Bacillus subtilis lytic bacteriophage ϕNIT1 capable of obstructing natto fermentation carrying genes for the capsule-lytic soluble enzymes poly-γ-glutamate hydrolase and levanase.

    Science.gov (United States)

    Ozaki, Tatsuro; Abe, Naoki; Kimura, Keitarou; Suzuki, Atsuto; Kaneko, Jun

    2017-01-01

    Bacillus subtilis strains including the fermented soybean (natto) starter produce capsular polymers consisting of poly-γ-glutamate and levan. Capsular polymers may protect the cells from phage infection. However, bacteriophage ϕNIT1 carries a γ-PGA hydrolase gene (pghP) that help it to counteract the host cell's protection strategy. ϕNIT had a linear double stranded DNA genome of 155,631-bp with a terminal redundancy of 5,103-bp, containing a gene encoding an active levan hydrolase. These capsule-lytic enzyme genes were located in the possible foreign gene cluster regions between central core and terminal redundant regions, and were expressed at the late phase of the phage lytic cycle. All tested natto origin Spounavirinae phages carried both genes for capsule degrading enzymes similar to ϕNIT1. A comparative genomic analysis revealed the diversity among ϕNIT1 and Bacillus phages carrying pghP-like and levan-hydrolase genes, and provides novel understanding on the acquisition mechanism of these enzymatic genes.

  14. Deletion of Lytic Transglycosylases Increases Beta-Lactam Resistance in Shewanella oneidensis

    Science.gov (United States)

    Yin, Jianhua; Sun, Yiyang; Sun, Yijuan; Yu, Zhiliang; Qiu, Juanping; Gao, Haichun

    2018-01-01

    Production of chromosome-encoded β-lactamases confers resistance to β-lactams in many Gram-negative bacteria. Some inducible β-lactamases, especially the class C β-lactamase AmpC in Enterobacteriaceae, share a common regulatory mechanism, the ampR-ampC paradigm. Induction of ampC is intimately linked to peptidoglycan recycling, and the LysR-type transcriptional regulator AmpR plays a central role in the process. However, our previous studies have demonstrated that the expression of class D β-lactamase gene blaA in Shewanella oneidensis is distinct from the established paradigm since an AmpR homolog is absent and major peptidoglycan recycling enzymes play opposite roles in β-lactamase expression. Given that lytic transglycosylases (LTs), a class of peptidoglycan hydrolases cleaving the β-1,4 glycosidic linkage in glycan strands of peptidoglycan, can disturb peptidoglycan recycling, and thus may affect induction of blaA. In this study, we investigated impacts of such enzymes on susceptibility to β-lactams. Deletion of three LTs (SltY, MltB and MltB2) increased β-lactam resistance, while four other LTs (MltD, MltD2, MltF, and Slt2) seemed dispensable to β-lactam resistance. The double LT mutants ΔmltBΔmltB2 and ΔsltYΔmltB2 had β-lactam resistance stronger than any of the single mutants. Deletion of ampG (encoding permease AmpG) and mrcA (encoding penicillin binding protein 1a, PBP1a) from both double LT mutants further increased the resistance to β-lactams. Notably, all increased β-lactam resistance phenotypes were in accordance with enhanced blaA expression. Although significant, the increase in β-lactamase activity after inactivating LTs is much lower than that produced by PBP1a inactivation. Our data implicate that LTs play important roles in blaA expression in S. oneidensis. PMID:29403465

  15. Bacteriophage and lytic enzymes - can they help us in the war with antibiotic resistant bacteria

    International Nuclear Information System (INIS)

    Trudil, D.; Rainina, E.

    2009-01-01

    Drug-resistant pathogens are a growing menace to all people, regardless of age, or socioeconomic background. They endanger people industrial societies like the United States, as well as in less developed nations and are even causing problems in military field hospitals. From Streptococcus pneumoniae to Staphylococcus, C. difficile, and multidrug-resistant TB, the list is growing. The threat of engineered microorganisms further complicates the interaction between man and Mother Nature. Additionally, although antibiotics were specifically designed for treating human health emergencies, their use for raising livestock animals has expanded. In the US, large amounts of antibiotics are routinely mixed into feed in order to promote growth rather than combat disease and as prophylactic treatment to offset unnatural diets and unhealthy living conditions. U.S.-raised animals in the 1950s received 2 million pounds per year of antibiotics in their feed compared to 50 million pounds today-a 2,500-percent increase. A large percentage of these drugs pass into the environment. In fact, prior to 1995, when fluoroquinolones were first approved to treat poultry, very few fluoroquinolone-resistant Campylobacter were found in people with foodborne diseases in the United States. After the approval, however, many more fluoroquinolone-resistant bacteria were found in humans and in poultry from slaughter plants and retail stores. The threat to our food supply becomes a threat to security. What can be done? One approach is to treat bacterial diseases by the use of bacteriophages. Phages are very small viruses that destroy by lysing select bacteria. The idea of using phage as a therapy for infectious bacterial diseases was first proposed by d'Herelle around World War I and over 80 years bacteriophage has been a key tool of healthcare professionals within Eastern Europe. More recently professionals in the USA and Western Europe have isolated and developed specific lytic components which have

  16. Composite Material Switches

    Science.gov (United States)

    Javadi, Hamid (Inventor)

    2002-01-01

    A device to protect electronic circuitry from high voltage transients is constructed from a relatively thin piece of conductive composite sandwiched between two conductors so that conduction is through the thickness of the composite piece. The device is based on the discovery that conduction through conductive composite materials in this configuration switches to a high resistance mode when exposed to voltages above a threshold voltage.

  17. MCT/MOSFET Switch

    Science.gov (United States)

    Rippel, Wally E.

    1990-01-01

    Metal-oxide/semiconductor-controlled thyristor (MCT) and metal-oxide/semiconductor field-effect transistor (MOSFET) connected in switching circuit to obtain better performance. Offers high utilization of silicon, low forward voltage drop during "on" period of operating cycle, fast turnon and turnoff, and large turnoff safe operating area. Includes ability to operate at high temperatures, high static blocking voltage, and ease of drive.

  18. Python Switch Statement

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available The Python programming language does not have a built in switch/case control structure as found in many other high level programming languages. It is thought by some that this is a deficiency in the language, and the control structure should be added. This paper demonstrates that not only is the control structure not needed, but that the methods available in Python are more expressive than built in case statements in other high level languages.

  19. Ferroelectric switching of elastin

    Science.gov (United States)

    Liu, Yuanming; Cai, Hong-Ling; Zelisko, Matthew; Wang, Yunjie; Sun, Jinglan; Yan, Fei; Ma, Feiyue; Wang, Peiqi; Chen, Qian Nataly; Zheng, Hairong; Meng, Xiangjian; Sharma, Pradeep; Zhang, Yanhang; Li, Jiangyu

    2014-01-01

    Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm2, whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications. PMID:24958890

  20. De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal Ganglia.

    Science.gov (United States)

    Sawtell, Nancy M; Thompson, Richard L

    2016-09-01

    The life long relationship between herpes simplex virus and its host hinges on the ability of the virus to aggressively replicate in epithelial cells at the site of infection and transport into the nervous system through axons innervating the infection site. Interaction between the virus and the sensory neuron represents a pivot point where largely unknown mechanisms lead to a latent or a lytic infection in the neuron. Regulation at this pivot point is critical for balancing two objectives, efficient widespread seeding of the nervous system and host survival. By combining genetic and in vivo in approaches, our studies reveal that the balance between latent and lytic programs is a process occurring early in the trigeminal ganglion. Unexpectedly, activation of the latent program precedes entry into the lytic program by 12 -14hrs. Importantly, at the individual neuronal level, the lytic program begins as a transition out of this acute stage latent program and this escape from the default latent program is regulated by de novo VP16 expression. Our findings support a model in which regulated de novo VP16 expression in the neuron mediates entry into the lytic cycle during the earliest stages of virus infection in vivo. These findings support the hypothesis that the loose association of VP16 with the viral tegument combined with sensory axon length and transport mechanisms serve to limit arrival of virion associated VP16 into neuronal nuclei favoring latency. Further, our findings point to specialized features of the VP16 promoter that control the de novo expression of VP16 in neurons and this regulation is a key component in setting the balance between lytic and latent infections in the nervous system.

  1. Volume of Lytic Vertebral Body Metastatic Disease Quantified Using Computed Tomography–Based Image Segmentation Predicts Fracture Risk After Spine Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thibault, Isabelle [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Centre Hospitalier de L' Universite de Québec–Université Laval, Quebec, Quebec (Canada); Whyne, Cari M. [Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, Department of Surgery, University of Toronto, Toronto, Ontario (Canada); Zhou, Stephanie; Campbell, Mikki [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Atenafu, Eshetu G. [Department of Biostatistics, University Health Network, University of Toronto, Toronto, Ontario (Canada); Myrehaug, Sten; Soliman, Hany; Lee, Young K. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Ebrahimi, Hamid [Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, Department of Surgery, University of Toronto, Toronto, Ontario (Canada); Yee, Albert J.M. [Division of Orthopaedic Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that would predict vertebral compression fracture (VCF) risk after stereotactic body radiation therapy (SBRT), using volumetric image-segmentation software. Methods and Materials: A computational semiautomated skeletal metastasis segmentation process refined in our laboratory was applied to the pretreatment planning CT scan of 100 vertebral segments in 55 patients treated with spine SBRT. Each VB was segmented and the percentage of lytic and/or blastic disease by volume determined. Results: The cumulative incidence of VCF at 3 and 12 months was 14.1% and 17.3%, respectively. The median follow-up was 7.3 months (range, 0.6-67.6 months). In all, 56% of segments were determined lytic, 23% blastic, and 21% mixed, according to clinical radiologic determination. Within these 3 clinical cohorts, the segmentation-determined mean percentages of lytic and blastic tumor were 8.9% and 6.0%, 0.2% and 26.9%, and 3.4% and 15.8% by volume, respectively. On the basis of the entire cohort (n=100), a significant association was observed for the osteolytic percentage measures and the occurrence of VCF (P<.001) but not for the osteoblastic measures. The most significant lytic disease threshold was observed at ≥11.6% (odds ratio 37.4, 95% confidence interval 9.4-148.9). On multivariable analysis, ≥11.6% lytic disease (P<.001), baseline VCF (P<.001), and SBRT with ≥20 Gy per fraction (P=.014) were predictive. Conclusions: Pretreatment lytic VB disease volumetric measures, independent of the blastic component, predict for SBRT-induced VCF. Larger-scale trials evaluating our software are planned to validate the results.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. A comparative study on the activity of fungal lytic polysaccharide monooxygenases for the depolymerization of cellulose in soybean spent flakes.

    Science.gov (United States)

    Pierce, Brian C; Agger, Jane Wittrup; Zhang, Zhenghong; Wichmann, Jesper; Meyer, Anne S

    2017-09-08

    Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes capable of the oxidative breakdown of polysaccharides. They are of industrial interest due to their ability to enhance the enzymatic depolymerization of recalcitrant substrates by glycoside hydrolases. In this paper, twenty-four lytic polysaccharide monooxygenases (LPMOs) expressed in Trichoderma reesei were evaluated for their ability to oxidize the complex polysaccharides in soybean spent flakes, an abundant and industrially relevant substrate. TrCel61A, a soy-polysaccharide-active AA9 LPMO from T. reesei, was used as a benchmark in this evaluation. In total, seven LPMOs demonstrated activity on pretreated soy spent flakes, with the products from enzymatic treatments evaluated using mass spectrometry and high performance anion exchange chromatography. The hydrolytic boosting effect of the top-performing enzymes was evaluated in combination with endoglucanase and beta-glucosidase. Two enzymes (TrCel61A and Aspte6) showed the ability to release more than 36% of the pretreated soy spent flake glucose - a greater than 75% increase over the same treatment without LPMO addition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Crystallization and preliminary X-ray diffraction analysis of the lytic transglycosylase MltE from Escherichia coli

    International Nuclear Information System (INIS)

    Artola-Recolons, Cecilia; Llarrull, Leticia I.; Lastochkin, Elena; Mobashery, Shahriar; Hermoso, Juan A.

    2010-01-01

    Crystals of the lytic transglycosylase MltE from E. coli were grown using the microbatch method and diffracted to a resolution of 2.1 Å. MltE from Escherichia coli (193 amino acids, 21 380 Da) is a lytic transglycosylase that initiates the first step of cell-wall recycling. This enzyme is responsible for the cleavage of the cell-wall peptidoglycan at the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units. At the end this reaction generates a disaccharide that is internalized and initiates the recycling process. To obtain insights into the biological functions of MltE, crystallization trials were performed and crystals of MltE protein that were suitable for X-ray diffraction analysis were obtained. The MltE protein of E. coli was crystallized using the hanging-drop vapour-diffusion method at 291 K. Crystals grew from a mixture consisting of 28% polyethylene glycol 4000, 0.1 M Tris pH 8.4 and 0.2 M magnesium chloride. Further optimization was performed using the microbatch technique. Single crystals were obtained that belonged to the orthorhombic space group C222 1 , with unit-cell parameters a = 123.32, b = 183.93, c = 35.29 Å, and diffracted to a resolution of 2.1 Å

  9. Listeria monocytogenes has a functional chitinolytic system and an active lytic polysaccharide monooxygenase

    DEFF Research Database (Denmark)

    Paspaliari, Dafni Katerina; Loose, Jennifer S. M.; Larsen, Marianne Halberg

    2015-01-01

    Chitinases and chitin-active lytic polysaccharide monooxygenases (LPMOs) are most commonly associated with chitin metabolism, but are also reported as virulence factors in pathogenic bacteria. Listeria monocytogenes, a well-known virulent bacterium, possesses two chitinases (ChiA and ChiB) and a ......Chitinases and chitin-active lytic polysaccharide monooxygenases (LPMOs) are most commonly associated with chitin metabolism, but are also reported as virulence factors in pathogenic bacteria. Listeria monocytogenes, a well-known virulent bacterium, possesses two chitinases (ChiA and Chi...... but different product profiles depending on the substrate. In LPMO-chitinase synergy experiments, CBP21 is able to boost the activity of both ChiA and ChiB more than LmLPMO10. Product analysis of the synergy assays revealed that the chitinases were unable to efficiently hydrolyse the LPMO products...... (chitooligosaccharide aldonic acids) with a degree of polymerization below four (ChiA and SmChiC) or three (ChiB). Gene transcription and protein expression analysis showed that LmLPMO10 is neither highly transcribed, nor abundantly secreted during the growth of L. monocytogenes in a chitin-containing medium...

  10. The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications.

    Science.gov (United States)

    Hu, Jianmin; Li, Hongde; Luo, Xiangjian; Li, Yueshuo; Bode, Ann; Cao, Ya

    2017-11-01

    Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. © 2017 UICC.

  11. Effective inhibition of lytic development of bacteriophages λ, P1 and T4 by starvation of their host, Escherichia coli

    Directory of Open Access Journals (Sweden)

    Węgrzyn Alicja

    2007-02-01

    Full Text Available Abstract Background Bacteriophage infections of bacterial cultures cause serious problems in genetic engineering and biotechnology. They are dangerous not only because of direct effects on the currently infected cultures, i.e. their devastation, but also due to a high probability of spreading the phage progeny throughout a whole laboratory or plant, which causes a real danger for further cultivations. Therefore, a simple method for quick inhibition of phage development after detection of bacterial culture infection should be very useful. Results Here, we demonstrate that depletion of a carbon source from the culture medium, which provokes starvation of bacterial cells, results in rapid inhibition of lytic development of three Escherichia coli phages, λ, P1 and T4. Since the effect was similar for three different phages, it seems that it may be a general phenomenon. Moreover, similar effects were observed in flask cultures and in chemostats. Conclusion Bacteriophage lytic development can be inhibited efficiently by carbon source limitation in bacterial cultures. Thus, if bacteriophage contamination is detected, starvation procedures may be recommended to alleviate deleterious effects of phage infection on the culture. We believe that this strategy, in combination with the use of automated and sensitive bacteriophage biosensors, may be employed in the fermentation laboratory practice to control phage outbreaks in bioprocesses more effectively.

  12. Efficient Translation of Epstein-Barr Virus (EBV) DNA Polymerase Contributes to the Enhanced Lytic Replication Phenotype of M81 EBV.

    Science.gov (United States)

    Church, Trenton Mel; Verma, Dinesh; Thompson, Jacob; Swaminathan, Sankar

    2018-03-15

    Epstein-Barr virus (EBV) is linked to the development of both lymphoid and epithelial malignancies worldwide. The M81 strain of EBV, isolated from a Chinese patient with nasopharyngeal carcinoma (NPC), demonstrates spontaneous lytic replication and high-titer virus production in comparison to the prototype B95-8 EBV strain. Genetic comparisons of M81 and B95-8 EBVs were previously been performed in order to determine if the hyperlytic property of M81 is associated with sequence differences in essential lytic genes. EBV SM is an RNA-binding protein expressed during early lytic replication that is essential for virus production. We compared the functions of M81 SM and B95-8 SM and demonstrate that polymorphisms in SM do not contribute to the lytic phenotype of M81 EBV. However, the expression level of the EBV DNA polymerase protein was much higher in M81- than in B95-8-infected cells. The relative deficiency in the expression of B95-8 DNA polymerase was related to the B95-8 genome deletion, which truncates the BALF5 3' untranslated region (UTR). Similarly, the insertion of bacmid DNA into the widely used recombinant B95-8 bacmid creates an inefficient BALF5 3' UTR. We further showed that the while SM is required for and facilitates the efficient expression of both M81 and B95-8 mRNAs regardless of the 3' UTR, the BALF5 3' UTR sequence is important for BALF5 protein translation. These data indicate that the enhanced lytic replication and virus production of M81 compared to those of B95-8 are partly due to the robust translation of EBV DNA polymerase required for viral DNA replication due to a more efficient BALF5 3' UTR in M81. IMPORTANCE Epstein-Barr virus (EBV) infects more than 90% of the human population, but the incidence of EBV-associated tumors varies greatly in different parts of the world. Thus, understanding the connection between genetic polymorphisms from patient isolates of EBV, gene expression phenotypes, and disease is important and may help in

  13. Comparison of MGIT and Myco/F lytic liquid-based blood culture systems for recovery of Mycobacterium tuberculosis from pleural fluid.

    Science.gov (United States)

    Harausz, Elizabeth; Lusiba, John Kafuluma; Nsereko, Mary; Johnson, John L; Toossi, Zahra; Ogwang, Sam; Boom, W Henry; Joloba, Moses L

    2015-04-01

    The specificities and sensitivities of the Bactec mycobacterial growth indicator tube (MGIT) system for the recovery of Mycobacterium tuberculosis from pleural fluid are not statistically different than those of the Myco/F lytic liquid culture system. The time to positivity is shorter in the MGIT system (12.7 versus 20.7 days, respectively; P=0.007). The Myco/F lytic culture system may be an alternative to the MGIT system for diagnosing pleural tuberculosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. 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.

  15. 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....

  16. 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).

  17. 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.

  18. 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.)

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. MENGAPA PERUSAHAAN MELAKUKAN AUDITOR SWITCH?

    Directory of Open Access Journals (Sweden)

    Kadek Sumadi

    2011-01-01

    Full Text Available The existence of a large number of accounting firms allowsprovides companies choices whether to stay with current firm or switchto another accounting firm. Decision of Minister of FinanceNo.423/KMK.06/2002 states that a company must switch auditor afterfive years of consecutive assignment. This is mandatory. The questionrises when a company voluntarily switches its auditor. Why does thishappen?One of the reasons is that management does not satisfy withauditor opinion, except for unqualified opinion. New management teamwould directly or indirectly encourage auditor switch to align accountingand reporting policies. Moreover an expanding company expects positivereaction when it does auditor switch. Profitability is also one reason fora company to switch auditor, for example, when a company earns moreprofit it tends to hire more credible auditor. On the other hand, when thecompany faces a financial distress, it probably would switch auditor aswell.

  6. Low-Crosstalk Composite Optical Crosspoint Switches

    Science.gov (United States)

    Pan, Jing-Jong; Liang, Frank

    1993-01-01

    Composite optical switch includes two elementary optical switches in tandem, plus optical absorbers. Like elementary optical switches, composite optical switches assembled into switch matrix. Performance enhanced by increasing number of elementary switches. Advantage of concept: crosstalk reduced to acceptably low level at moderate cost of doubling number of elementary switches rather than at greater cost of tightening manufacturing tolerances and exerting more-precise control over operating conditions.

  7. Compound semiconductor optical waveguide switch

    Science.gov (United States)

    Spahn, Olga B.; Sullivan, Charles T.; Garcia, Ernest J.

    2003-06-10

    An optical waveguide switch is disclosed which is formed from III-V compound semiconductors and which has a moveable optical waveguide with a cantilevered portion that can be bent laterally by an integral electrostatic actuator to route an optical signal (i.e. light) between the moveable optical waveguide and one of a plurality of fixed optical waveguides. A plurality of optical waveguide switches can be formed on a common substrate and interconnected to form an optical switching network.

  8. Neuromorphic atomic switch networks.

    Directory of Open Access Journals (Sweden)

    Audrius V Avizienis

    Full Text Available Efforts to emulate the formidable information processing capabilities of the brain through neuromorphic engineering have been bolstered by recent progress in the fabrication of nonlinear, nanoscale circuit elements that exhibit synapse-like operational characteristics. However, conventional fabrication techniques are unable to efficiently generate structures with the highly complex interconnectivity found in biological neuronal networks. Here we demonstrate the physical realization of a self-assembled neuromorphic device which implements basic concepts of systems neuroscience through a hardware-based platform comprised of over a billion interconnected atomic-switch inorganic synapses embedded in a complex network of silver nanowires. Observations of network activation and passive harmonic generation demonstrate a collective response to input stimulus in agreement with recent theoretical predictions. Further, emergent behaviors unique to the complex network of atomic switches and akin to brain function are observed, namely spatially distributed memory, recurrent dynamics and the activation of feedforward subnetworks. These devices display the functional characteristics required for implementing unconventional, biologically and neurally inspired computational methodologies in a synthetic experimental system.

  9. 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.

  10. Recent developments in switching theory

    CERN Document Server

    Mukhopadhyay, Amar

    2013-01-01

    Electrical Science Series: Recent Developments in Switching Theory covers the progress in the study of the switching theory. The book discusses the simplified proof of Post's theorem on completeness of logic primitives; the role of feedback in combinational switching circuits; and the systematic procedure for the design of Lupanov decoding networks. The text also describes the classical results on counting theorems and their application to the classification of switching functions under different notions of equivalence, including linear and affine equivalences. The development of abstract har

  11. Software Switching for Data Acquisition

    CERN Multimedia

    CERN. Geneva; Malone, David

    2016-01-01

    In this talk we discuss the feasibility of replacing telecom-class routers with a topology of commodity servers acting as software switches in data acquisition. We extend the popular software switch, Open vSwitch, with a dedicated, throughput-oriented buffering mechanism. We compare the performance under heavy many-to-one congestion to typical Ethernet switches and evaluate the scalability when building larger topologies, exploiting the integration with software-defined networking technologies. Please note that David Malone will speak on behalf of Grzegorz Jereczek.

  12. Decalcified allograft in repair of lytic lesions of bone: A study to evolve bone bank in developing countries

    Directory of Open Access Journals (Sweden)

    Anil Kumar Gupta

    2016-01-01

    Full Text Available Background: The quest for ideal bone graft substitutes still haunts orthopedic researchers. The impetus for this search of newer bone substitutes is provided by mismatch between the demand and supply of autogenous bone grafts. Bone banking facilities such as deep frozen and freeze-dried allografts are not so widely available in most of the developing countries. To overcome the problem, we have used partially decalcified, ethanol preserved, and domestic refrigerator stored allografts which are economical and needs simple technology for procurement, preparation, and preservation. The aim of the study was to assess the radiological and functional outcome of the partially decalcified allograft (by weak hydrochloric acid in patients of benign lytic lesions of bone. Through this study, we have also tried to evolve, establish, and disseminate the concept of the bone bank. Materials and Methods: 42 cases of lytic lesions of bone who were treated by decalcified (by weak hydrochloric acid, ethanol preserved, allografts were included in this prospective study. The allograft was obtained from freshly amputated limbs or excised femoral heads during hip arthroplasties under strict aseptic conditions. The causes of lytic lesions were unicameral bone cyst ( n = 3, aneurysmal bone cyst ( n = 3, giant cell tumor ( n = 9, fibrous dysplasia ( n = 12, chondromyxoid fibroma, chondroma, nonossifying fibroma ( n = 1 each, tubercular osteomyelitis ( n = 7, and chronic pyogenic osteomyelitis ( n = 5. The cavity of the lesion was thoroughly curetted and compactly filled with matchstick sized allografts. Results: Quantitative assessment based on the criteria of Sethi et al. (1993 was done. There was complete assimilation in 27 cases, partial healing in 12 cases, and failure in 3 cases. Functional assessment was also done according to which there were 29 excellent results, 6 good, and 7 cases of failure (infection, recurrence, and nonunion of pathological fracture. We

  13. MUREIN-METABOLIZING ENZYMES FROM ESCHERICHIA-COLI - SEQUENCE-ANALYSIS AND CONTROLLED OVEREXPRESSION OF THE SLT GENE, WHICH ENCODES THE SOLUBLE LYTIC TRANSGLYCOSYLASE

    NARCIS (Netherlands)

    ENGEL, H; KAZEMIER, B; KECK, W

    The complete nucleotide sequence of the slt gene encoding the soluble lytic transglycosylase (Slt; EC 3.2.1.-) from Escherichia coli has been determined. The largest open reading frame identified on a 2.5-kb PvuII-SalI fragment indicates that the enzyme is translated as a preprotein of either 654 or

  14. Latent and lytic HHV-8 mRNA expression in PBMCs and Kaposi's sarcoma skin biopsies of AIDS Kaposi's sarcoma patients

    NARCIS (Netherlands)

    Polstra, Abeltje M.; Goudsmit, Jaap; Cornelissen, Marion

    2003-01-01

    Human herpes virus 8 (HHV-8) is associated with all clinical forms of Kaposi's sarcoma. HHV-8 DNA is present in Kaposi's sarcoma biopsies and is observed regularly in saliva and less consistently in blood of Kaposi's sarcoma patients. The expression pattern of latent (ORF 73) and lytic (vGCR,

  15. Development of real-time NASBA assays with molecular beacon detection to quantify mRNA coding for HHV-8 lytic and latent genes

    NARCIS (Netherlands)

    Polstra, Abeltje M.; Goudsmit, J.; Cornelissen, M.

    2002-01-01

    Background: Human herpesvirus-8 (HHV-8) is linked to the pathogenesis of Kaposi's sarcoma (KS), and the HHV-8 DNA load in peripheral blood mononuclear cells ( PBMC) is associated with the clinical stage of KS. To examine the expression of HHV-8 in PBMC, four HHV-8 mRNA specific NASBA assays were

  16. Hybrid switch for resonant power converters

    Science.gov (United States)

    Lai, Jih-Sheng; Yu, Wensong

    2014-09-09

    A hybrid switch comprising two semiconductor switches connected in parallel but having different voltage drop characteristics as a function of current facilitates attainment of zero voltage switching and reduces conduction losses to complement reduction of switching losses achieved through zero voltage switching in power converters such as high-current inverters.

  17. LCT protective dump-switch tests

    International Nuclear Information System (INIS)

    Parsons, W.M.

    1981-01-01

    Each of the six coils in the Large Coil Task (LCT) has a separate power supply, dump resistor, and switching circuit. Each switching circuit contains five switches, two of which are redundant. The three remaining switches perform separate duties in an emergency dump situation. These three switches were tested to determine their ability to meet the LCT conditions

  18. Oxidative cleavage and hydrolytic boosting of cellulose in soybean spent flakes by Trichoderma reesei Cel61A lytic polysaccharide monooxygenase.

    Science.gov (United States)

    Pierce, Brian C; Agger, Jane Wittrup; Wichmann, Jesper; Meyer, Anne S

    2017-03-01

    The auxiliary activity family 9 (AA9) copper-dependent lytic polysaccharide monooxygenase (LPMO) from Trichoderma reesei (EG4; TrCel61A) was investigated for its ability to oxidize the complex polysaccharides from soybean. The substrate specificity of the enzyme was assessed against a variety of substrates, including both soy spent flake, a by-product of the soy food industry, and soy spent flake pretreated with sodium hydroxide. Products from enzymatic treatments were analyzed using mass spectrometry and high performance anion exchange chromatography. We demonstrate that TrCel61A is capable of oxidizing cellulose from both pretreated soy spent flake and phosphoric acid swollen cellulose, oxidizing at both the C1 and C4 positions. In addition, we show that the oxidative activity of TrCel61A displays a synergistic effect capable of boosting endoglucanase activity, and thereby substrate depolymerization of soy cellulose, by 27%. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Role of protein kinase C in TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells.

    Science.gov (United States)

    Abraha, Abraham B; Rana, Krupa; Whalen, Margaret M

    2010-11-01

    Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposure of NK cells to tributyltin (TBT) greatly diminishes their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C(PKC) as well as MAPK activity. TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposure. TBT caused a 2–3-fold activation of PKC at concentrations ranging from 50 to 300 nM (16–98 ng/ml),indicating that activation of PKC occurs in response to TBT exposure. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells, validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that, in NK cells where PKC activation was blocked, there was no activation of the MAPK, p44/42 in response to TBT.However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including activation of p44/42 by TBT in NK cells.

  20. Role of protein kinase C in the TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells

    Science.gov (United States)

    Abraha, Abraham B.; Rana, Krupa; Whalen, Margaret M.

    2010-01-01

    Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposures of NK cells to tributyltin (TBT) greatly diminish their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in the NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C (PKC) as well as MAPK activity. The TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in the inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposures. TBT caused a 2–3 fold activation of PKC at concentrations ranging from 50–300 nM (16–98 ng/mL), indicating that activation of PKC occurs in response to TBT exposures. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that in NK cells where PKC activation was blocked there was no activation of the MAPK, p44/42 in response to TBT. However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including the activation of p44/42 by TBT in NK cells. PMID:20390410

  1. Combined Inhibition of the BMP pathway and the RANK-RANKL axis in a Mixed Lytic/blastic Prostate Cancer Lesion

    Science.gov (United States)

    Virk, Mandeep S.; Alaee, Farhang; Petrigliano, Frank A.; Sugiyama, Osamu; Chatziioannou, Arion F.; Stout, David; Dougall, William C.; Lieberman, Jay R.

    2010-01-01

    The purpose of this study was to investigate the influence of combined inhibition of RANKL (receptor activator of nuclear factor kappa-B ligand) and bone morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer lesion in bone. Human prostate cancer cells (C4 2b) were injected into immunocompromised mice using an intratibial injection model to create mixed lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent formation, function and survival of osteoclasts. Inhibition of BMP activity was achieved by transducing prostate cancer cells ex vivo with a retroviral vector expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc treatment, RN treatment and combined RN and RANK-Fc treatment) and two control groups (untreated control and empty vector control for the RN treatment group). The progression of bone lesion and tumor growth was evaluated using plain radiographs, hind limb tumor size, 18F-Fluorodeoxyglucose and 18F-fluoride micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone inhibited osteolysis and transformed a mixed lytic/blastic lesion into an osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic component in a mixed lytic/blastic lesion and resulted in formation of smaller osteolytic bone lesion with smaller soft tissue size. The animals treated with both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition of osteolysis, small soft tissue tumors and preservation of bone architecture with less tumor induced new bone formation. This study suggests that combined inhibition of the RANKL and the BMP pathway may be an effective biologic therapy to inhibit the progression of established mixed lytic/blastic prostate cancer lesions in bone. PMID:21073986

  2. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    Science.gov (United States)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

  3. Circuit switched optical networks

    DEFF Research Database (Denmark)

    Kloch, Allan

    2003-01-01

    Some of the most important components required for enabling optical networking are investigated through both experiments and modelling. These all-optical components are the wavelength converter, the regenerator and the space switch. When these devices become "off-the-shelf" products, optical cross......, it is expected that the optical solution will offer an economical benefit for hight bit rate networks. This thesis begins with a discussion of the expected impact on communications systems from the rapidly growing IP traffic, which is expected to become the dominant source for traffic. IP traffic has some...... characteristics, which are best supported by an optical network. The interest for such an optical network is exemplified by the formation of the ACTS OPEN project which aim was to investigate the feasibility of an optical network covering Europe. Part of the work presented in this thesis is carried out within...

  4. Photo-switching element

    Energy Technology Data Exchange (ETDEWEB)

    Masaki, Yuichi

    1987-10-31

    Photo-input MOS transistor (Photo-switching element) cannot give enough ON/OFF ratio but requires an auxiliary condenser for a certain type of application. In addition, PN junction of amorphous silicon is not practical because it gives high leak current resulting in low electromotive force. In this invention, a solar cell was constructed with a lower electrode consisting of a transparent electro-conducting film, a photosensitive part consisting of an amorphous Si layer of p-i-n layer construction, and an upper metal electrode consisting of Cr or Nichrome, and a thin film transistor was placed on the solar cell, and further the upper metal electrode was co-used as a gate electrode of the thin film transistor; this set-up of this invention enabled to attain an efficient photo-electric conversion of the incident light, high electromotive force of the solar cell, and the transistor with high ON/OFF ratio. (3 figs)

  5. Battery switch for downhole tools

    Science.gov (United States)

    Boling, Brian E.

    2010-02-23

    An electrical circuit for a downhole tool may include a battery, a load electrically connected to the battery, and at least one switch electrically connected in series with the battery and to the load. The at least one switch may be configured to close when a tool temperature exceeds a selected temperature.

  6. Improved switch-resistor packaging

    Science.gov (United States)

    Redmerski, R. E.

    1980-01-01

    Packaging approach makes resistors more accessible and easily identified with specific switches. Failures are repaired more quickly because of improved accessibility. Typical board includes one resistor that acts as circuit breaker, and others are positioned so that their values can be easily measured when switch is operated. Approach saves weight by using less wire and saves valuable panel space.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Superconductivity, energy storage and switching

    International Nuclear Information System (INIS)

    Laquer, H.L.

    1974-01-01

    The phenomenon of superconductivity can contribute to the technology of energy storage and switching in two distinct ways. On one hand the zero resistivity of the superconductor can produce essentially infinite time constants so that an inductive storage system can be charged from very low power sources. On the other hand, the recovery of finite resistivity in a normal-going superconducting switch can take place in extremely short times, so that a system can be made to deliver energy at a very high power level. Topics reviewed include: physics of superconductivity, limits to switching speed of superconductors, physical and engineering properties of superconducting materials and assemblies, switching methods, load impedance considerations, refrigeration economics, limitations imposed by present day and near term technology, performance of existing and planned energy storage systems, and a comparison with some alternative methods of storing and switching energy. (U.S.)

  9. Amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.; Smith, Casey; Hussain, Muhammad Mustafa

    2013-01-01

    Nanoelectromechanical (NEM) switch is an interesting ultra-low power option which can operate in the harsh environment and can be a complementary element in complex digital circuitry. Although significant advancement is happening in this field, report on ultra-low voltage (pull-in) switch which offers high switching speed and area efficiency is yet to be made. One key challenge to achieve such characteristics is to fabricate nano-scale switches with amorphous metal so the shape and dimensional integrity are maintained to achieve the desired performance. Therefore, we report a tungsten alloy based amorphous metal with fabrication process development of laterally actuated dual gated NEM switches with 100 nm width and 200 nm air-gap to result in <5 volts of actuation voltage (Vpull-in). © 2013 IEEE.

  10. Amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-04-01

    Nanoelectromechanical (NEM) switch is an interesting ultra-low power option which can operate in the harsh environment and can be a complementary element in complex digital circuitry. Although significant advancement is happening in this field, report on ultra-low voltage (pull-in) switch which offers high switching speed and area efficiency is yet to be made. One key challenge to achieve such characteristics is to fabricate nano-scale switches with amorphous metal so the shape and dimensional integrity are maintained to achieve the desired performance. Therefore, we report a tungsten alloy based amorphous metal with fabrication process development of laterally actuated dual gated NEM switches with 100 nm width and 200 nm air-gap to result in <5 volts of actuation voltage (Vpull-in). © 2013 IEEE.

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Switching Phenomena in a System with No Switches

    Science.gov (United States)

    Preis, Tobias; Stanley, H. Eugene

    2010-02-01

    It is widely believed that switching phenomena require switches, but this is actually not true. For an intriguing variety of switching phenomena in nature, the underlying complex system abruptly changes from one state to another in a highly discontinuous fashion. For example, financial market fluctuations are characterized by many abrupt switchings creating increasing trends ("bubble formation") and decreasing trends ("financial collapse"). Such switching occurs on time scales ranging from macroscopic bubbles persisting for hundreds of days to microscopic bubbles persisting only for a few seconds. We analyze a database containing 13,991,275 German DAX Future transactions recorded with a time resolution of 10 msec. For comparison, a database providing 2,592,531 of all S&P500 daily closing prices is used. We ask whether these ubiquitous switching phenomena have quantifiable features independent of the time horizon studied. We find striking scale-free behavior of the volatility after each switching occurs. We interpret our findings as being consistent with time-dependent collective behavior of financial market participants. We test the possible universality of our result by performing a parallel analysis of fluctuations in transaction volume and time intervals between trades. We show that these financial market switching processes have properties similar to those of phase transitions. We suggest that the well-known catastrophic bubbles that occur on large time scales—such as the most recent financial crisis—are no outliers but single dramatic representatives caused by the switching between upward and downward trends on time scales varying over nine orders of magnitude from very large (≈102 days) down to very small (≈10 ms).

  14. 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.

  15. 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.

  16. Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

    Science.gov (United States)

    Feng, Pinghui; Moses, Ashlee; Früh, Klaus

    2015-01-01

    γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Meningoencefalite por herpesvírus bovino-5 Meningoencephalitis by bovine herpesvirus-5

    Directory of Open Access Journals (Sweden)

    Daniel R. Rissi

    2007-07-01

    testar sorologicamente os bovinos a serem introduzidos nos rebanhos, minimizar situações de estresse, sobretudo no desmame, e isolamento dos bovinos afetados.Meningoencephalitis caused by bovine herpesvirus-5 (BoHV-5 is an often fatal, acute or subacute infectious disease that affects mainly young cattle under stressing conditions. The disease has been recognized in several Brazilian regions and in other parts of the world. BoHV-5 is a double stranded DNA virus member of the Herpesviridae family and subfamily Alphaherpesvirinae. The virus is characterized by rapid and lytic replication in cell cultures and by the ability to establish lifelong latent infection in sensory nerve ganglia of the host. BoHV-5 is transmitted mainly by direct and indirect contact and replicates acutely in the oral, nasal, oropharingeal or ocular mucosae. After primary replication, the virus invades nerve endings and is transported to the neuron cell bodies of the sensory ganglia where it replicates actively and/or establishes latency. Viral invasion of the brain may result in massive virus replication and production of neurological disease. Virtually all cattle developing neurological disease die of meningoencephalitis; yet the infection may be subclinical in some animals. These animals recover and become latently infected. Viral dissemination within a herd is facilitated by conditions such as crowding, introduction of cattle from other herds and weaning of calves in ages that coincide with decrease of passive immunity. Certain natural or induced conditions may reactivate the latent virus and favor its transmission and dissemination to other susceptible individuals. The disease may occur as outbreaks or as sporadic cases, with morbidity rates ranging of 0.05%-5%; lethality is almost always 100%. Clinical signs include depression, nasal and ocular discharge, grinding of teeth, circling, blindness, fever, paddling movements, disphagia, abdominal pain, nystagmus, muscle tremors, drooling

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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....

  8. 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.

  9. 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...

  10. DETERMINANT OF DOWNWARD AUDITOR SWITCHING

    Directory of Open Access Journals (Sweden)

    Totok Budisantoso

    2017-12-01

    Full Text Available Abstract: Determinant of Downward Auditor Switching. This study examines the factors that influence downward auditor switching in five ASEAN countries. Fixed effect logistic regression was used as analytical method. This study found that opinion shopping occurred in ASEAN, especially in distress companies. Companies with complex businesses will retain the Big Four auditors to reduce complexity and audit costs. Audit and public committees serve as guardians of auditor quality. On the other hand, shareholders failed to maintain audit quality. It indicates that there is entrenchment effect in auditor switching.

  11. Electrically switched ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M.A. [Pacific Northwest National Lab., Richland, WA (United States); Schwartz, D.T.; Genders, D.

    1997-10-01

    A variety of waste types containing radioactive {sup 137}Cs are found throughout the DOE complex. These waste types include water in reactor cooling basins, radioactive high-level waste (HLW) in underground storage tanks, and groundwater. Safety and regulatory requirements and economics require the removal of radiocesium before these wastes can be permanently disposed of. Electrically Switched Ion Exchange (ESIX) is an approach for radioactive cesium separation that combines IX and electrochemistry to provide a selective, reversible, and economic separation method that also produces little or no secondary waste. In the ESIX process, an electroactive IX film is deposited electrochemically onto a high-surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. For cesium, the electroactive films under investigation are ferrocyanides, which are well known to have high selectivities for cesium in concentrated sodium solutions. When a cathode potential is applied to the film, Fe{sup +3} is reduced to the Fe{sup +2} state, and a cation must be intercalated into the film to maintain charge neutrality (i.e., Cs{sup +} is loaded). Conversely, if an anodic potential is applied, a cation must be released from the film (i.e., Cs{sup +} is unloaded). Therefore, to load the film with cesium, the film is simply reduced; to unload cesium, the film is oxidized.

  12. 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

  13. High current vacuum closing switch

    International Nuclear Information System (INIS)

    Dolgachev, G.I.; Maslennikov, D.D.; Romanov, A.S.; Ushakov, A.G.

    2005-01-01

    The paper proposes a powerful pulsed closing vacuum switch for high current commutation consisting of series of the vacuum diodes with near 1 mm gaps having closing time determined by the gaps shortening with the near-electrode plasmas [ru

  14. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [State Univ. of New York (SUNY), Plattsburgh, NY (United States); Univ. of California, Davis, CA (United States)

    2012-01-20

    Photoconductive semiconductor switches (PCSS) have been investigated since the late 1970s. Some devices have been developed that withstand tens of kilovolts and others that switch hundreds of amperes. However, no single device has been developed that can reliably withstand both high voltage and switch high current. Yet, photoconductive switches still hold the promise of reliable high voltage and high current operation with subnanosecond risetimes. Particularly since good quality, bulk, single crystal, wide bandgap semiconductor materials have recently become available. In this chapter we will review the basic operation of PCSS devices, status of PCSS devices and properties of the wide bandgap semiconductors 4H-SiC, 6H-SiC and 2H-GaN.

  15. Switching of chirality by light

    NARCIS (Netherlands)

    Feringa, B.L.; Schoevaars, A.M; Jager, W.F.; de Lange, B.; Huck, N.P.M.

    1996-01-01

    Optically active photoresponsive molecules are described by which control of chirality is achieved by light. These chiroptical molecular switches are based on inherently dissymmetric overcrowded alkenes and the synthesis, resolution and dynamic stereochemical properties are discussed. Introduction

  16. Aurora oil switch upgrade program

    International Nuclear Information System (INIS)

    Warren, T.

    1989-03-01

    This report describes the short pulse synchronization requirements, the original Aurora trigger scheme, and the PI/SNLA approach to improving the synchronization. It also describes the oil switching design study undertaken as the first phase of the program. A discussion of oil-switch closure analysis and the conceptual design motivated by this analysis are presented. This paper also describes the oil-switch trigger pulser tests required to validate the concept. This includes the design of the testing facility, a description of the test goals, and a discussion of the results. This paper finally describes oil-switch trigger pulser testing on one of the four Aurora Blumlein modules, which includes the hardware design and operation, the testing goals, hardware installation, and test results. 9 refs., 26 figs

  17. Solid state bistable power switch

    Science.gov (United States)

    Bartko, J.; Shulman, H.

    1970-01-01

    Tin and copper provide high current and switching time capabilities for high-current resettable fuses. They show the best performance for trip current and degree of reliability, and have low coefficients of thermal expansion.

  18. Intrinsic nanofilamentation in resistive switching

    KAUST Repository

    Wu, Xing; Cha, Dong Kyu; Bosman, Michel; Raghavan, Nagarajan; Migas, Dmitri B.; Borisenko, Victor E.; Zhang, Xixiang; Li, Kun; Pey, Kin-Leong

    2013-01-01

    -chip circuitry and non-volatile memory storage. Here, we provide insight into the mechanisms that govern highly reproducible controlled resistive switching via a nanofilament by using an asymmetric metal-insulator-semiconductor structure. In-situ transmission

  19. Electron collisions in gas switches

    International Nuclear Information System (INIS)

    Christophorou, L.G.

    1989-01-01

    Many technologies rely on the conduction/insulation properties of gaseous matter for their successful operation. Many others (e.g., pulsed power technologies) rely on the rapid change (switching or modulation) of the properties of gaseous matter from an insulator to a conductor and vice versa. Studies of electron collision processes in gases aided the development of pulsed power gas switches, and in this paper we shall briefly illustrate the kind of knowledge on electron collision processes which is needed to optimize the performance of such switching devices. To this end, we shall refer to three types of gas switches: spark gap closing, self-sustained diffuse discharge closing, and externally-sustained diffuse discharge opening. 24 refs., 15 figs., 2 tabs

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Potency of Garlic Extract Against Koi Herpesvirus (KHV in Common Carp

    Directory of Open Access Journals (Sweden)

    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

  18. Cloning of Bovine herpesvirus type 1 and type 5 as infectious bacterial artifical chromosomes

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Equine herpesvirus 2 (EHV-2 infection in thoroughbred horses in Argentina

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  3. 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

  4. 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...

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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...

  16. 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...

  17. 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...

  18. 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

  19. A Piezoelectric Cryogenic Heat Switch

    Science.gov (United States)

    Jahromi, Amir E.; Sullivan, Dan F.

    2014-01-01

    We have measured the thermal conductance of a mechanical heat switch actuated by a piezoelectric positioner, the PZHS (PieZo electric Heat Switch), at cryogenic temperatures. The thermal conductance of the PZHS was measured between 4 K and 10 K, and on/off conductance ratios greater than 100 were achieved when the positioner applied its maximum force of 8 N. We discuss the advantages of using this system in cryogenic applications, and estimate the ultimate performance of an optimized PZHS.

  20. High PRF high current switch

    Science.gov (United States)

    Moran, Stuart L.; Hutcherson, R. Kenneth

    1990-03-27

    A triggerable, high voltage, high current, spark gap switch for use in pu power systems. The device comprises a pair of electrodes in a high pressure hydrogen environment that is triggered by introducing an arc between one electrode and a trigger pin. Unusually high repetition rates may be obtained by undervolting the switch, i.e., operating the trigger at voltages much below the self-breakdown voltage of the device.