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Sample records for virus latent origin

  1. Characterization of a Latent Virus-Like Infection of Symbiotic Zooxanthellae▿

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B.; Wilson, William H.

    2007-01-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms. PMID:17351090

  2. Characterization of a latent virus-like infection of symbiotic zooxanthellae.

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B; Wilson, William H

    2007-05-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms.

  3. Characterization of Chemokine Receptor Utilization of Viruses in the Latent Reservoir for Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Pierson, Theodore; Hoffman, Trevor L.; Blankson, Joel; Finzi, Diana; Chadwick, Karen; Margolick, Joseph B.; Buck, Christopher; Siliciano, Janet D.; Doms, Robert W.; Siliciano, Robert F.

    2000-01-01

    Latently infected resting CD4+ T cells provide a long-term reservoir for human immunodeficiency virus type 1 (HIV-1) and are likely to represent the major barrier to virus eradication in patients on combination antiretroviral therapy. The mechanisms by which viruses enter the latent reservoir and the nature of the chemokine receptors involved have not been determined. To evaluate the phenotype of the virus in this compartment with respect to chemokine receptor utilization, full-length HIV-1 env genes were cloned from latently infected cells and assayed functionally. We demonstrate that the majority of the viruses in the latent reservoir utilize CCR5 during entry, although utilization of several other receptors, including CXCR4, was observed. No alternative coreceptors were shown to be involved in a systematic fashion. Although R5 viruses are present in the latent reservoir, CCR5 was not expressed at high levels on resting CD4+ T cells. To understand the mechanism by which R5 viruses enter latent reservoir, the ability of an R5 virus, HIV-1 Ba-L, to infect highly purified resting CD4+ T lymphocytes from uninfected donors was evaluated. Entry of Ba-L could be observed when virus was applied at a multiplicity approaching 1. However, infection was limited to a subset of cells expressing low levels of CCR5 and markers of immunologic memory. Naive cells could not be infected by an R5 virus even when challenged with a large inoculum. Direct cell fractionation studies showed that latent virus is present predominantly in resting memory cells but also at lower levels in resting naive cells. Taken together, these findings provide support for the hypothesis that the direct infection of naive T cells is not the major mechanism by which the latent infection of resting T cells is established. PMID:10933689

  4. Role for a region of helically unstable DNA within the Epstein-Barr virus latent cycle origin of DNA replication oriP in origin function

    International Nuclear Information System (INIS)

    Polonskaya, Zhanna; Benham, Craig J.; Hearing, Janet

    2004-01-01

    The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA replication oriP is composed of two binding sites for the Epstein-Barr virus nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere repeat binding factor TRF2. Although not required for minimal replicator activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary elements located to the right of the EBNA-1/TRF2 sites are required for the efficient replication of oriP plasmids. Another region of oriP that is predicted to be destabilized by DNA supercoiling is shown here to be an important functional component of oriP. The ability of DNA fragments of unrelated sequence and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but not fragments characterized by helically stable DNA, to substitute for this component of oriP demonstrates a role for the SIDD region in the initiation of oriP-plasmid DNA replication

  5. Photodynamic inactivation of rubella virus enhances recombination with a latent virus of a baby hamster kidney cell line BHK21

    International Nuclear Information System (INIS)

    Yamamoto, Nobuto; Urade, Masahiro

    1989-01-01

    Rubella virus is very sensitive to photodynamic action. When tested with 1.2 x 10 -5 M toluidine blue and 8 W fluorescent lamp at a fluence of 11 W/m 2 , inactivation kinetics showed a linear single hit curve with a k value of 1.48 min -1 . Photodynamic inactivation of rubella virus greatly enhanced recombination with a latent virus (R-virus) of baby hamster kidney BHK21 cells. In contrast, no hybrids were detected in lysates of the cells infected with either UV-treated or untreated rubella virus. Therefore, hybrid viruses were readily detected only in lysates of BHK21 cells infected with photodynamically treated rubella virus. Photodynamic damage of rubella virus genomes generated a new hybrid type (hybrid type 3) in addition to a previously described type 2 hybrid (formerly designated as HPV-RV variant). Although both of these hybrid types carry the CF antigens of rubella virus, plaque forming ability of type 3 hybrid is neutralized neither by anti-rubella serum nor by anti-latent virus serum while type 2 hybrid is neutralized by anti-latent virus serum. (author)

  6. Epstein-Barr Virus: The Path from Latent to Productive Infection.

    Science.gov (United States)

    Chiu, Ya-Fang; Sugden, Bill

    2016-09-29

    The intrinsic properties of different viruses have driven their study. For example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. Epstein-Barr virus, another herpesvirus, has two properties that have driven its study: It causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. Here, we review our understanding of the path Epstein-Barr virus follows to move from a latent infection to and through its productive cycle. We use information from human infections to provide a framework for describing studies in cell culture and, where possible, the molecular resolutions from these studies. We also pose questions whose answers we think are pivotal to understanding this path, and we provide answers where we can.

  7. Latent Virus Reactivation in Space Shuttle Astronauts

    Science.gov (United States)

    Mehta, S. K.; Crucian, B. E.; Stowe, R. P.; Sams, C.; Castro, V. A.; Pierson, D. L.

    2011-01-01

    Latent virus reactivation was measured in 17 astronauts (16 male and 1 female) before, during, and after short-duration Space Shuttle missions. Blood, urine, and saliva samples were collected 2-4 months before launch, 10 days before launch (L-10), 2-3 hours after landing (R+0), 3 days after landing (R+14), and 120 days after landing (R+120). Epstein-Barr virus (EBV) DNA was measured in these samples by quantitative polymerase chain reaction. Varicella-zoster virus (VZV) DNA was measured in the 381 saliva samples and cytomegalovirus (CMV) DNA in the 66 urine samples collected from these subjects. Fourteen astronauts shed EBV DNA in 21% of their saliva samples before, during, and after flight, and 7 astronauts shed VZV in 7.4% of their samples during and after flight. It was interesting that shedding of both EBV and VZV increased during the flight phase relative to before or after flight. In the case of CMV, 32% of urine samples from 8 subjects contained DNA of this virus. In normal healthy control subjects, EBV shedding was found in 3% and VZV and CMV were found in less than 1% of the samples. The circadian rhythm of salivary cortisol measured before, during, and after space flight did not show any significant difference between flight phases. These data show that increased reactivation of latent herpes viruses may be associated with decreased immune system function, which has been reported in earlier studies as well as in these same subjects (data not reported here).

  8. Development of molecular tests for the detection of ILAR and latent viruses in fruit trees.

    Science.gov (United States)

    Roussel, S; Kummert, J; Dutrecq, O; Lepoivre, P; Jijakli, M H

    2004-01-01

    The detection throughout the year of latent and ILAR viruses in fruit tress by classical serological tests appear to be unreliable. We have developed RT-PCR tests for a reliable detection of latent and ILAR viruses in fruit trees. These assays were then simplified to allow the direct use of crude plant extracts instead of total RNA preparations, and the analyses of pooled samples. In this way, such RT-PCR protocols are suitable for a routine diagnosis of latent and ILAR viruses in fruit tree certification.

  9. Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.

    Science.gov (United States)

    McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G

    2012-05-01

    Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

  10. Space Flight-Induced Reactivation of Latent Epstein-Barr Virus

    Science.gov (United States)

    Stowe, Raymond P.; Barrett, Alan D. T.; Pierson, Duane L.

    2001-01-01

    Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. We hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B-lymphocytes. If increased virus production and clonal expansion of infected B-lymphocytes are detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease. More importantly, we will begin to understand the basic mechanisms involved in stress-induced reactivation of EBV in circulating B-lymphocytes.

  11. Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes

    Directory of Open Access Journals (Sweden)

    Brian G. Murphy

    2012-05-01

    Full Text Available Feline immunodeficiency virus (FIV, the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

  12. 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.

  13. Reactivation of Latent Epstein-Barr Virus; A Comparison After Gamma Rays and Proton Treatment

    Science.gov (United States)

    Mehta, Satish K.; Plante, Ianik; Bloom, David C.; Stowe, Raymond; Renner, Ashlie; Wu, Honglu; Crucian, Brian; Pierson, Duane L.

    2017-01-01

    Among different unique stressors astronauts are exposed to during spaceflight, cosmic radiation constitutes an important one that leads to various health effects. In particular, space radiation may contribute to decreased immunity, which has been observed in astronauts during short and long duration missions, as evidenced by several changes in cellular immunity and plasma cytokines levels. Reactivation of latent herpes viruses, either directly from radiation or resulting from perturbation in the immune system, is also observed in astronauts. While EBV is one of the eight human herpes viruses known to infect more than 90% human adults and stays latent for the life of the host without normally causing adverse effects of reactivation, increased reactivation in astronauts is well-documented, though the mechanism of this increase is not understood. In this work, we have studied the effect of two different types of radiations, Cs-137 gamma and 150-MeV proton on the reactivation rates of the Epstein - Barr virus (EBV) in vitro in EBV latent cell lines at doses of 0.1, 0.5, 1.0 and 2.0 Gy. While we find that both types of radiations reactivated latent EBV in vitro, we observe that at equivalent doses, early response is stronger for protons but with time, the reactivation induced by gamma rays is more persistent. These differences between the protons and gamma rays curves in latent virus reactivation challenge the common paradigm that protons and gamma rays have similar biological effects.

  14. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    Science.gov (United States)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

  15. Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

    Science.gov (United States)

    Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

    2017-07-01

    Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

  16. Development and characterization of the first infectious clone of alfalfa latent virus, a strain of Pea streak virus

    Science.gov (United States)

    Alfalfa (Medicago sativa) is a natural host plant for many plant pathogens including fungi, bacteria, nematodes and viruses. Alfalfa latent virus (ALV) is a member of the carlavirus group and occurs symptomlessly in alfalfa. The first complete genomic sequence of the ALV that was recently obtained i...

  17. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

  18. Complete genome sequence of currant latent virus (genus Cheravirus, family Secoviridae)

    Czech Academy of Sciences Publication Activity Database

    Petrzik, Karel; Koloniuk, Igor; Přibylová, Jaroslava; Špak, Josef

    2016-01-01

    Roč. 161, č. 2 (2016), s. 491-493 ISSN 0304-8608 Institutional support: RVO:60077344 Keywords : Stranded-RNA * complete genome sequence * Currant latent virus Subject RIV: EE - Microbiology, Virology Impact factor: 2.058, year: 2016

  19. Epstein-Barr virus latent gene sequences as geographical markers of viral origin: unique EBNA3 gene signatures identify Japanese viruses as distinct members of the Asian virus family.

    Science.gov (United States)

    Sawada, Akihisa; Croom-Carter, Deborah; Kondo, Osamu; Yasui, Masahiro; Koyama-Sato, Maho; Inoue, Masami; Kawa, Keisei; Rickinson, Alan B; Tierney, Rosemary J

    2011-05-01

    Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.

  20. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans.

    Science.gov (United States)

    Efstathiou, S; Minson, A C; Field, H J; Anderson, J R; Wildy, P

    1986-02-01

    Herpes simplex virus-specific DNA sequences have been detected by Southern hybridization analysis in both central and peripheral nervous system tissues of latently infected mice. We have detected virus-specific sequences corresponding to the junction fragment but not the genomic termini, an observation first made by Rock and Fraser (Nature [London] 302:523-525, 1983). This "endless" herpes simplex virus DNA is both qualitatively and quantitatively stable in mouse neural tissue analyzed over a 4-month period. In addition, examination of DNA extracted from human trigeminal ganglia has shown herpes simplex virus DNA to be present in an "endless" form similar to that found in the mouse model system. Further restriction enzyme analysis of latently infected mouse brainstem and human trigeminal DNA has shown that this "endless" herpes simplex virus DNA is present in all four isomeric configurations.

  1. Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

    Science.gov (United States)

    Menges, Steven A; Riepe, Joshua R; Philips, Gary T

    2015-09-01

    A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms. Using Aplysia, we have studied the mechanisms of savings due to latent memory for a prior, forgotten experience. We previously reported savings in the induction of three distinct temporal domains of memory: short-term (10min), intermediate-term (2h) and long-term (24h). Here we report that savings memory formation utilizes molecular signaling pathways that are distinct from original learning: whereas the induction of both original intermediate- and long-term memory in naïve animals requires mitogen activated protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings memory is not dependent on MAPK activation. Collectively, these findings reveal that during forgetting, latent memory for the original experience can facilitate relearning through molecular signaling mechanisms that are distinct from original learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Poinsettia latent virus is not a cryptic virus, but a natural polerovirus-sobemovirus hybrid

    International Nuclear Information System (INIS)

    Siepen, Marc aus dem; Pohl, Jens O.; Koo, Bong-Jin; Wege, Christina; Jeske, Holger

    2005-01-01

    The biochemical and genetic features of Poinsettia latent virus (PnLV, formerly named Poinsettia cryptic virus), which is spread worldwide in commercial cultivars of Euphorbia pulcherrima without inducing symptoms, have been determined using virus-purification, immunological techniques, electron microscopy, cloning, and sequencing. PnLV was found to be a chimeric virus with one 4652 bases, plus strand RNA showing a close relationship to poleroviruses within the first three quarters of its genome but to sobemoviruses in the last quarter. Thus, we propose to classify this virus as 'polemovirus'. Similarities of protein and nucleic acid sequences at the 5' and extreme 3' end of its RNA suggest a replication mode like that of poleroviruses, whereas the coat protein sequence is closely related to that of sobemoviruses. Consistent with these results, PnLV forms stable icosahedra of 34 nm in diameter. The consequences for the taxonomy of PnLV and for gardeners' practice are discussed

  3. EBNA1 efficiently assembles on chromatin containing the Epstein-Barr virus latent origin of replication

    International Nuclear Information System (INIS)

    Avolio-Hunter, Tina M.; Frappier, Lori

    2003-01-01

    The Epstein-Barr virus (EBV) protein, EBNA1, activates the replication of latent EBV episomes and the transcription of EBV latency genes by binding to recognition sites in the DS and FR elements of oriP. Since EBV episomes exist as chromatin, we have examined the interaction of EBNA1 with oriP templates assembled with physiologically spaced nucleosomes. We show that EBNA1 retains the ability to efficiently bind its recognition sites within the DS and FR elements in oriP chromatin and that this property is intrinsic to the EBNA1 DNA binding domain. The efficient assembly of EBNA1 on oriP chromatin does not require ATP-dependent chromatin remodeling factors and does not cause the precise positioning of nucleosomes within or adjacent to the FR and DS elements. Thus EBNA1 belongs to a select group of proteins that can efficiently access their recognition sites within nucleosomes without the need for additional chromatin remodeling factors

  4. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Xiaozhen Liang

    2009-11-01

    Full Text Available Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68 gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners that do not directly participate in virus replication, but rather facilitate virus

  5. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Science.gov (United States)

    Liang, Xiaozhen; Collins, Christopher M; Mendel, Justin B; Iwakoshi, Neal N; Speck, Samuel H

    2009-11-01

    Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68) gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency) account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners) that do not directly participate in virus replication, but rather facilitate virus reactivation by

  6. Latent Virus Reactivation in Astronauts and Shingles Patients

    Science.gov (United States)

    Mehta, Satish K.; Cohrs, Randall J.; Gilden, Donald H.; Tyring, Stephen K.; Castro, Victoria A.; Ott, C. Mark; Pierson, Duane L.

    2010-01-01

    Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpesviruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpes viruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

  7. The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure.

    Science.gov (United States)

    Ranganath, Nischal; Sandstrom, Teslin S; Burke Schinkel, Stephanie C; Côté, Sandra C; Angel, Jonathan B

    2018-02-14

    Cells latently infected with human immunodeficiency virus (HIV) evade immune- and drug-mediated clearance. These cells harbor intracellular signaling defects, including impairment of the antiviral type I interferon response. Such defects have also been observed in several cancers and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate cells latently infected with HIV-1, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in cell lines latently infected with HIV-1. Following this, a reduction in HIV-1 DNA and inducible HIV-1 replication was observed following MG1 infection of latently infected, resting CD4+ T cells generated using an in vitro model of latency. Last, MG1 infection resulted in a reduction in HIV-1 DNA and inducible HIV-1 replication in memory CD4+ T cells isolated from effectively treated, HIV-1-infected individuals. Our results therefore highlight a novel approach to eliminate the latent HIV-1 reservoir. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  8. Ekspresi produk gen laten virus epstein-barr pada karsinoma sel skuamosa rongga mulut (The expressions of latent gene product of epstein-barr virus in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Theresia Indah Budhy S

    2005-06-01

    Full Text Available Squamous cell carcinoma (SCC is a type of cancer often found in oral cavity and the area of head and neck at about 90%. Based on the geographical incidence oral SCC (OSCC has many types of different emerging. This case probably has connection with ethnic group, habit and social and economical condition. In East Java, the incidence is about 2.64% and it increases every year. The virus is known as one of the main factors that result in this disease. Epstein-Barr virus (EBV has potential capability of carcinogenesis. EBV is the family of herpesviridae that can infect cell through the linking of CD 21 receptor of the epithel with glycol protein 350/220 of the virus capsule. After primary infection, the virus will form latent-gene in human cell. Periodically, the latent-gene product can disturb proliferation and apoptotic regulator. In Indonesia, the expression of EBV latent geneproduct in the OSCC has not been reported yet. This study wanted to know the expression of EBV latent gene product found in the OSCC. This study found 25 cases of OSCC in which 17 were infected by EBV. Detection of EBV infection could be done by insitu hybridization to identify RNA EBV (EBER. To find the expression of EBV latent gene product, immunohistochemical analysis was done. The conclusion was that the emerging of expression of EBV latent gene product in OSCC were latent membrane protein-1 (LMP-1, EBV nuclear antigen-1 (EBNA-1 and RNA EBV (EBER. They were 28.28%, 25.26% and 46.47%. It was suggested to do the following research on OSCC infected by EBV and the emerging of expression of EBV latent gene product with regulator gene of proliferation and apoptotic in OSCC.

  9. Stimulation of HIV-1-specific cytolytic T-lymphocytes facilitates elimination of latent viral reservoir after virus reactivation

    Science.gov (United States)

    Shan, Liang; Deng, Kai; Shroff, Neeta S.; Durand, Christine; Rabi, S. Alireza.; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B.; Blankson, Joel N.; Siliciano, Robert F.

    2012-01-01

    Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia. Life-long treatment is therefore required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T-cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4+ T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T-lymphocytes (CTL) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials. PMID:22406268

  10. Latent Virus Reactivation: From Space to Earth

    Science.gov (United States)

    Mehta, Satish K.; Cohrs, Randall J.; Gilden, Donald H.; Tyring, Stephen K.; Castro, Victoria A.; Ott, C. Mark; Pierson, Duane L.

    2010-01-01

    Reactivation of latent viruses is a recognized consequence of decreased immunity. More recently viral reactivation has been identified as an important in vivo indicator of clinically relevant immune changes. Viral reactivation can be determined quickly and easily by the presence of virus in saliva and other body fluids. Real-time polymerase chain reaction (PCR) is a highly sensitive and specific molecular method to detect the presence of specific viral DNA. Studies in astronauts demonstrated that herpes simplex virus type 1(HSV-1), Epstein-Barr Virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate at rates above normal during and after spaceflight in response to moderately decreased T-cell immunity. This technology was expanded to patients on Earth beginning with human immune deficiency virus (HIV) immuno-compromised patients. The HIV patients shed EBV in saliva at rates 9-fold higher than observed in astronauts demonstrating that the level of EBV shedding reflects the severity of impaired immunity. Whereas EBV reactivation is not expected to produce serious effects in astronauts on missions of 6 months or less, VZV reactivation in astronauts could produce shingles. Reactivation of live, infectious VZV in astronauts with no symptoms was demonstrated in astronauts during and after spaceflight. We applied our technology to study VZV-induced shingles in patients. In a study of 54 shingles patients, we showed salivary VZV was present in every patient on the day antiviral (acyclovir) treatment was initiated. Pain and skin lesions decreased with antiviral treatment. Corresponding decreases in levels of VZV were also observed and accompanied recovery. Although the level of VZV in shingles patients before the treatment was generally higher than those found in astronauts, lower range of VZV numbers in shingles patients overlapped with astronaut s levels. This suggests a potential risk of shingles to astronauts resulting from reactivation of VZV. In

  11. Next generation sequencing and molecular analysis of artichoke Italian latent virus.

    Science.gov (United States)

    Elbeaino, Toufic; Belghacem, Imen; Mascia, Tiziana; Gallitelli, Donato; Digiaro, Michele

    2017-06-01

    Next-generation sequencing (NGS) allowed the assembly of the complete RNA-1 and RNA-2 sequences of a grapevine isolate of artichoke Italian latent virus (AILV). RNA-1 and RNA-2 are 7,338 and 4,630 nucleotides in length excluding the 3' terminal poly(A) tail, and encode two putative polyproteins of 255.8 kDa (p1) and 149.6 kDa (p2), respectively. All conserved motifs and predicted cleavage sites, typical for nepovirus polyproteins, were found in p1 and p2. AILV p1 and p2 share high amino acid identity with their homologues in beet ringspot virus (p1, 81% and p2, 71%), tomato black ring virus (p1, 79% and p2, 63%), grapevine Anatolian ringspot virus (p1, 65% and p2, 63%), and grapevine chrome mosaic virus (p1, 60% and p2, 54%), and to a lesser extent with other grapevine nepoviruses of subgroup A and C. Phylogenetic and sequence analyses, all confirmed the strict relationship of AILV with members classified in subgroup B of genus Nepovirus.

  12. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    International Nuclear Information System (INIS)

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-01-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation

  13. Detection of yellow dwarf virus onion (OYDV) and garlic common latent virus (GCLV) in Costa Rican garlic (Allium sativum L)

    International Nuclear Information System (INIS)

    Guillen Watson, Anny Vannesa; Chacon Cerdas, Randall; Zuniga Vega, Claudia

    2011-01-01

    Viral diseases have been responsible for significant losses in crop yield of garlic in the world. Costa Rican material Garlic has been analyzed to determine the incidence of : onion yellow dwarf virus (OYDV), the leek yellow stripe virus (LYSV), shallot latent virus (SLV) and garlic common latent virus (GLCV). The DAS-ELISA technique has been used for status native plant material. Bulbs field apparently normal (N), normal with yellow tunic (TA) and deformed (D) and normal field sheets (N), symptomatic (S) and possible presence of viral vectors (VT) were used. Vitroplants product have analyzed the introduction of apices of 1,0 and 0,5 cm in length teeth from normal (N) and yellow tunic (TA). The 33% of the bulbs GCLV field were analyzed for positive (TA), whereas OYDV was detected 100% appearance regardless. 100% of the plantlets have presented without infection of GCLV, the OYDV only those introduced in apices of 1,0 cm from bulbs with yellow robes have shown without effect. GCLV is determined for 100% of the samples for both batches OYDV bulb formation in vitro and in only 50%. In the Costa Rican garlic has concluded that are present the viruses of GCLV and OYDV, with a high incidence on local material and differential infection according to the organ analyzed. Various methodologies combined are recommended together with the apexes vitro cultivation, for more effective viral clearance and thus increase the value and boost the local seed crop. (author) [es

  14. Original antigenic sin responses to influenza viruses.

    Science.gov (United States)

    Kim, Jin Hyang; Skountzou, Ioanna; Compans, Richard; Jacob, Joshy

    2009-09-01

    Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original Ag" rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.

  15. A built-in co-carcinogenic effect due to viruses involved in latent or persistent infections

    DEFF Research Database (Denmark)

    Hersoug, Lars-Georg; Arnau, José

    2007-01-01

    instability. Because of chromosomal instability, the genome of these cell lines will lead to changes from generation to generation and will face a remarkable selection pressure both from lost traits, apoptosis, and from the immune system. Viruses causing latent or persistent infections have evolved many...

  16. Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

    Science.gov (United States)

    Diaz, Fernando M; Knipe, David M

    2016-01-15

    Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV Vulnerable to Clearance by CD8 T Cells

    Directory of Open Access Journals (Sweden)

    Julia A. Sung

    2017-09-01

    Full Text Available Latently human immunodeficiency virus (HIV-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA. The LCA is a quantitative viral outgrowth assay (QVOA that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period. Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms.

  18. [Origin and evolution of human immunodeficiency viruses].

    Science.gov (United States)

    Marian, Constantin V

    2009-01-01

    After the diagnosis of the AIDS symptoms, in 1981, and after the discovery of the virus that causes AIDS, in 1983, the virologists have formulated different theories about its origin. Some of them involved natural causes, e.g., HIV origin from SIV strains. Other theories go further to the possibility of a deadly man-made virus escaped from laboratories or voluntary spread by some conspirative organisations. At this moment, the scientists limits themselves to search proofs to sustain the zoonotic origin of HIV from SIV and its accomodation to human body conditions.

  19. Brazilian Vaccinia Viruses and Their Origins

    Centers for Disease Control (CDC) Podcasts

    Smallpox was eradicated more than 25 years ago, but live viruses used in vaccines may have survived to cause animal and human illness today. Dr. Inger Damon, Acting Branch Chief of the Poxvirus and Rabies Branch at CDC, discusses efforts to determine origins and spread of vaccinia viruses in Brazil.

  20. Porphyromonas endodontalis reactivates latent Epstein-Barr virus.

    Science.gov (United States)

    Makino, K; Takeichi, O; Imai, K; Inoue, H; Hatori, K; Himi, K; Saito, I; Ochiai, K; Ogiso, B

    2018-06-01

    To determine whether Porphyromonas endodontalis can reactivate latent Epstein-Barr virus (EBV). The concentrations of short-chain fatty acids (SCFAs) in P. endodontalis culture supernatants were determined using high-performance liquid chromatography. A promoter region of BamHI fragment Z leftward open reading frame 1 (BZLF-1), which is a transcription factor that controls the EBV lytic cycle, was cloned into luciferase expression vectors. Then, the luciferase assay was performed using P. endodontalis culture supernatants. Histone acetylation using Daudi cells treated with P. endodontalis culture supernatants was examined using Western blotting. BZLF-1 mRNA and BamHI fragment Z EB replication activator (ZEBRA) protein were also detected quantitatively using real-time polymerase chain reaction (PCR) and Western blotting. Surgically removed periapical granulomas were examined to detect P. endodontalis, EBV DNA, and BZLF-1 mRNA expression using quantitative real-time PCR. Statistical analysis using Steel tests was performed. The concentrations of n-butyric acid in P. endodontalis culture supernatants were significantly higher than those of other SCFAs (P=0.0173). Using B-95-8-221 Luc cells treated with P. endodontalis culture supernatants, the luciferase assay demonstrated that P. endodontalis induced BZLF-1 expression. Hyperacetylation of histones was also observed with the culture supernatants. BZLF-1 mRNA and ZEBRA protein were expressed by Daudi cells in a dose-dependent manner after the treatment with P. endodontalis culture supernatants. P. endodontalis and BZLF-1 in periapical granulomas were also detected. The expression levels of BZLF-1 mRNA were similar to the numbers of P. endodontalis cells in each specimen. n-butyric acid produced by P. endodontalis reactivated latent EBV. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Large Amounts of Reactivated Virus in Tears Precedes Recurrent Herpes Stromal Keratitis in Stressed Rabbits Latently Infected with Herpes Simplex Virus.

    Science.gov (United States)

    Perng, Guey-Chuen; Osorio, Nelson; Jiang, Xianzhi; Geertsema, Roger; Hsiang, Chinhui; Brown, Don; BenMohamed, Lbachir; Wechsler, Steven L

    2016-01-01

    Recurrent herpetic stromal keratitis (rHSK), due to an immune response to reactivation of herpes simplex virus (HSV-1), can cause corneal blindness. The development of therapeutic interventions such as drugs and vaccines to decrease rHSK have been hampered by the lack of a small and reliable animal model in which rHSK occurs at a high frequency during HSV-1 latency. The aim of this study is to develop a rabbit model of rHSK in which stress from elevated temperatures increases the frequency of HSV-1 reactivations and rHSK. Rabbits latently infected with HSV-1 were subjected to elevated temperatures and the frequency of viral reactivations and rHSK were determined. In an experiment in which rabbits latently infected with HSV-1 were subjected to ill-defined stress as a result of failure of the vivarium air conditioning system, reactivation of HSV-1 occurred at over twice the normal frequency. In addition, 60% of eyes developed severe rHSK compared to tears of that eye and whenever this unusually large amount of reactivated virus was detected in tears, rHSK always appeared 4-5 days later. In subsequent experiments using well defined heat stress the reactivation frequency was similarly increased, but no eyes developed rHSK. The results reported here support the hypothesis that rHSK is associated not simply with elevated reactivation frequency, but rather with rare episodes of very high levels of reactivated virus in tears 4-5 days earlier.

  2. 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.

  3. Brazilian Vaccinia Viruses and Their Origins

    Centers for Disease Control (CDC) Podcasts

    2007-07-30

    Smallpox was eradicated more than 25 years ago, but live viruses used in vaccines may have survived to cause animal and human illness today. Dr. Inger Damon, Acting Branch Chief of the Poxvirus and Rabies Branch at CDC, discusses efforts to determine origins and spread of vaccinia viruses in Brazil.  Created: 7/30/2007 by Emerging Infectious Diseases.   Date Released: 7/30/2007.

  4. Molecular characterization and prevalence of two capulaviruses: Alfalfa leaf curl virus from France and Euphorbia caput-medusae latent virus from South Africa.

    Science.gov (United States)

    Bernardo, Pauline; Muhire, Brejnev; François, Sarah; Deshoux, Maëlle; Hartnady, Penelope; Farkas, Kata; Kraberger, Simona; Filloux, Denis; Fernandez, Emmanuel; Galzi, Serge; Ferdinand, Romain; Granier, Martine; Marais, Armelle; Monge Blasco, Pablo; Candresse, Thierry; Escriu, Fernando; Varsani, Arvind; Harkins, Gordon W; Martin, Darren P; Roumagnac, Philippe

    2016-06-01

    Little is known about the prevalence, diversity, evolutionary processes, genomic structures and population dynamics of viruses in the divergent geminivirus lineage known as the capulaviruses. We determined and analyzed full genome sequences of 13 Euphorbia caput-medusae latent virus (EcmLV) and 26 Alfalfa leaf curl virus (ALCV) isolates, and partial genome sequences of 23 EcmLV and 37 ALCV isolates. While EcmLV was asymptomatic in uncultivated southern African Euphorbia caput-medusae, severe alfalfa disease symptoms were associated with ALCV in southern France. The prevalence of both viruses exceeded 10% in their respective hosts. Besides using patterns of detectable negative selection to identify ORFs that are probably functionally expressed, we show that ALCV and EcmLV both display evidence of inter-species recombination and biologically functional genomic secondary structures. Finally, we show that whereas the EcmLV populations likely experience restricted geographical dispersion, ALCV is probably freely moving across the French Mediterranean region. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Theories about evolutionary origins of human hepatitis B virus in primates and humans.

    Science.gov (United States)

    Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

    2014-01-01

    The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

  6. Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

    Science.gov (United States)

    Sinha, Mahua; Rao, Clementina Rama; Premalata, C S; Shafiulla, Mohammed; Lakshmaiah, K C; Jacob, Linu Abraham; Babu, Govind K; Viveka, B K; Appaji, L; Subramanyam, Jayshree R

    2016-01-01

    There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

  7. Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2.

    Science.gov (United States)

    Umbach, Jennifer L; Wang, Kening; Tang, Shuang; Krause, Philip R; Mont, Erik K; Cohen, Jeffrey I; Cullen, Bryan R

    2010-01-01

    Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (U(L)) region of the genome, 3' to the U(L)15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT.

  8. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation.

    Science.gov (United States)

    Kennedy, Peter G E; Rovnak, Joel; Badani, Hussain; Cohrs, Randall J

    2015-07-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an 'end-less' state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is increasing

  9. Origins and evolution of viruses of eukaryotes: The ultimate modularity

    International Nuclear Information System (INIS)

    Koonin, Eugene V.; Dolja, Valerian V.; Krupovic, Mart

    2015-01-01

    Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources

  10. Origins and evolution of viruses of eukaryotes: The ultimate modularity

    Energy Technology Data Exchange (ETDEWEB)

    Koonin, Eugene V., E-mail: koonin@ncbi.nlm.nih.gov [National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894 (United States); Dolja, Valerian V., E-mail: doljav@science.oregonstate.edu [Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331 (United States); Krupovic, Mart, E-mail: krupovic@pasteur.fr [Institut Pasteur, Unité Biologie Moléculaire du Gène chez les Extrêmophiles, Department of Microbiology, Paris 75015 (France)

    2015-05-15

    Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources

  11. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    2014-09-01

    Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

  12. Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2▿

    Science.gov (United States)

    Umbach, Jennifer L.; Wang, Kening; Tang, Shuang; Krause, Philip R.; Mont, Erik K.; Cohen, Jeffrey I.; Cullen, Bryan R.

    2010-01-01

    Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (UL) region of the genome, 3′ to the UL15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT. PMID:19889786

  13. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice.

    Science.gov (United States)

    Field, H J; Bell, S E; Elion, G B; Nash, A A; Wildy, P

    1979-04-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.

  14. Evolutionary origins of hepatitis A virus in small mammals.

    Science.gov (United States)

    Drexler, Jan Felix; Corman, Victor M; Lukashev, Alexander N; van den Brand, Judith M A; Gmyl, Anatoly P; Brünink, Sebastian; Rasche, Andrea; Seggewiβ, Nicole; Feng, Hui; Leijten, Lonneke M; Vallo, Peter; Kuiken, Thijs; Dotzauer, Andreas; Ulrich, Rainer G; Lemon, Stanley M; Drosten, Christian

    2015-12-08

    Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3D(pol) sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses.

  15. Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein-Barr Virus Latent Phase Protein LMP1.

    Science.gov (United States)

    Lomakin, Ya A; Shmidt, A A; Bobik, T V; Chernov, A S; Pyrkov, A Yu; Aleksandrova, N M; Okunola, D O; Vaskina, M I; Ponomarenko, N A; Telegin, G B; Dubina, M V; Belogurov, A A

    2017-10-01

    Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein.

  16. Effect of Acycloguanosine Treatment on Acute and Latent Herpes Simplex Infections in Mice

    Science.gov (United States)

    Field, Hugh J.; Bell, Susanne E.; Elion, Gertrude B.; Nash, Anthony A.; Wildy, Peter

    1979-01-01

    Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form. PMID:464587

  17. Influenza A Viruses of Human Origin in Swine, Brazil.

    Science.gov (United States)

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.

  18. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

    Science.gov (United States)

    Kennedy, Peter G. E.; Rovnak, Joel; Badani, Hussain

    2015-01-01

    Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an ‘end-less’ state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is

  19. Identification of a new class of small molecules that efficiently reactivate latent Epstein-Barr virus

    Science.gov (United States)

    Tikhmyanova, Nadezhda; Schultz, David C.; Lee, Theresa; Salvino, Joseph M.; Lieberman, Paul M.

    2014-01-01

    Epstein-Barr Virus (EBV) persists as a latent infection in many lymphoid and epithelial malignancies, including Burkitt's lymphomas, nasopharyngeal carcinomas, and gastric carcinomas. Current chemotherapeutic treatments of EBV-positive cancers include broad- spectrum cytotoxic drugs that ignore the EBV-positive status of tumors. An alternative strategy, referred to as oncolytic therapy, utilizes drugs that stimulate reactivation of latent EBV to enhance the selective killing of EBV positive tumors, especially in combination with existing inhibitors of herpesvirus lytic replication, like Ganciclovir (GCV). At present, no small molecule, including histone deacetylase (HDAC) inhibitors, have proven safe or effective in clinical trials for treatment of EBV positive cancers. Aiming to identify new chemical entities that induce EBV lytic cycle, we have developed a robust high throughput cell-based assay to screen 66,840 small molecule compounds. Five structurally related tetrahydrocarboline derivatives were identified, two of which had EC50 measurements in the range of 150-170 nM. We show that these compounds reactivate EBV lytic markers ZTA and EA-D in all EBV-positive cell lines we have tested independent of the type of latency. The compounds reactivate a higher percentage of latently infected cells than HDAC inhibitors or phorbol esters in many cell types. The most active compounds showed low toxicity to EBV-negative cells, but were highly effective at selective cell killing of EBV-positive cells when combined with GCV. We conclude that we have identified a class of small molecule compounds that are highly effective at reactivating latent EBV infection in a variety of cell types, and show promise for lytic therapy in combination with GCV. PMID:24028149

  20. Influenza A Viruses of Human Origin in Swine, Brazil

    Science.gov (United States)

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  1. Original article Latent classes of criminal intent associated with criminal behaviour

    Directory of Open Access Journals (Sweden)

    Daniel Boduszek

    2014-07-01

    Full Text Available Background This study aimed to examine the number of latent classes of criminal intent that exist among prisoners and to look at the associations with recidivism, number of police arrests, type of offending (robbery, violent offences, murder, and multiple offences, and age. Participants and procedure Latent class analysis was used to identify homogeneous subgroups of prisoners based on their responses to the 10 questions reflecting criminal intent. Participants were 309 male recidivistic prisoners incarcerated in a maximum security prison. Multinomial logistic regression was used to interpret the nature of the latent classes, or groups, by estimating the association between recidivism and latent classes of criminal intent while controlling for offence type (robbery, violent offences, murder, and multiple offences, number of arrests, and age. Results The best fitting latent class model was a three-class solution: ‘High criminal intent’ (49.3%, ‘Intermediate criminal intent’ (41.3%, and ‘Low criminal intent’ (9.4%. The latent classes were differentially related to the external variables (recidivism, violent offences, and age. Conclusions Criminal intent is best explained by three homogeneous classes that appear to represent an underlying continuum. Future work is needed to identify whether these distinct classes of criminal intent may predict engagement in various types of criminal behaviour.

  2. Herpes simplex virus type 2 latency in the footpad of mice: effect of acycloguanosine on the recovery of virus.

    Science.gov (United States)

    Al-Saadi, S A; Gross, P; Wildy, P

    1988-02-01

    Herpes simplex virus type 2 has been reactivated from the latent state in the footpad and dorsal root ganglia of acycloguanosine-treated BALB/c mice. Virus was also recovered from the footpad tissue but not from the ganglia of denervated, latently infected mice. Treatment in vitro of explanted footpad cultures with acycloguanosine or phosphonoacetic acid did not affect the rate of virus reactivation. In all the isolates examined the virus was found to be acycloguanosine-sensitive. Recovery of virus from footpad tissue of mice after a long period of acycloguanosine treatment supports the theory that virus had been truly latent in the footpad and not in a state of persistent infection.

  3. An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.

    Science.gov (United States)

    Tang, Shuang; Bertke, Andrea S; Patel, Amita; Wang, Kening; Cohen, Jeffrey I; Krause, Philip R

    2008-08-05

    Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.

  4. Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region

    DEFF Research Database (Denmark)

    Sandvej, Kristian; Gratama, J W; Munch, M

    1997-01-01

    Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which...... include loss of a Xho I restriction site (position 169425) and a C-terminal 30-base pair (bp) deletion (position 168287-168256), define EBV genotypes associated with increased tumorigenicity or with disease among particular geographic populations. To determine the frequency of LMP-1 variations in European...... wild-type virus isolates, we sequenced the LMP-1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D...

  5. The p19 protein of Grapevine Algerian latent virus is a determinant of systemic infection of Chenopodium quinoa.

    Science.gov (United States)

    Kim, Semin; Cho, Won Kyong; Lee, Hyeok-Geun; Park, Sang-Ho; Sohn, Seong-Han; Kim, Kook-Hyung

    2012-04-01

    A previous study showed that both Grapevine Algerian latent virus (GALV) and Tomato bushy stunt virus (TBSV) systemically infect Nicotiana benthamiana, but GALV causes systemic infection whereas TBSV causes only local lesions in Chenopodium quinoa (C. quinoa). We recently isolated GALV strain Naju (GALV-N) from Limonium sinense and TBSV strain Sacheon (TBSV-S) from tomato. Both viruses belong to the genus Tombusvirus and have a similar genome organization. To identify determinants of systemic infection of GALV-N in C. quinoa in the current study, we generated infectious clones and capsid protein (CP)-deletion clones for the two viruses and confirmed that CP of GALV-N is required for systemic infection of C. quinoa due to its primary structural role in virus assembly. Through the use of chimeras, we identified a viral factor in addition to CP that contributes to systemic infection by GALV-N. Inactivation of the p19 demonstrated that host-specific activities of p19 are necessary for efficient systemic infection of C. quinoa by GALV-N. Our study is the first report to determine the viral factors required for systemic infection of GALV in C. quinoa. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus.

    Science.gov (United States)

    Zhu, Henan; Hughes, Joseph; Murcia, Pablo R

    2015-05-01

    Influenza A viruses (IAVs) are maintained mainly in wild birds, and despite frequent spillover infections of avian IAVs into mammals, only a small number of viruses have become established in mammalian hosts. A new H3N2 canine influenza virus (CIV) of avian origin emerged in Asia in the mid-2000s and is now circulating in dog populations of China and South Korea, and possibly in Thailand. The emergence of CIV provides new opportunities for zoonotic infections and interspecies transmission. We examined 14,764 complete IAV genomes together with all CIV genomes publicly available since its first isolation until 2013. We show that CIV may have originated as early as 1999 as a result of segment reassortment among Eurasian and North American avian IAV lineages. We also identified amino acid changes that might have played a role in CIV emergence, some of which have not been previously identified in other cross-species jumps. CIV evolves at a lower rate than H3N2 human influenza viruses do, and viral phylogenies exhibit geographical structure compatible with high levels of local transmission. We detected multiple intrasubtypic and heterosubtypic reassortment events, including the acquisition of the NS segment of an H5N1 avian influenza virus that had previously been overlooked. In sum, our results provide insight into the adaptive changes required by avian viruses to establish themselves in mammals and also highlight the potential role of dogs to act as intermediate hosts in which viruses with zoonotic and/or pandemic potential could originate, particularly with an estimated dog population of ∼ 700 million. Influenza A viruses circulate in humans and animals. This multihost ecology has important implications, as past pandemics were caused by IAVs carrying gene segments of both human and animal origin. Adaptive evolution is central to cross-species jumps, and this is why understanding the evolutionary processes that shape influenza A virus genomes is key to elucidating

  7. Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1

    Science.gov (United States)

    Piret, Jocelyne; Lamontagne, Julie; Désormeaux, André; Bergeron, Michel G.

    2001-01-01

    The influence of sodium lauryl sulfate (SLS) on the efficacies of gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous lesions and on the establishment and reactivation of latent virus has been evaluated in a murine model of orofacial infection. Topical treatments were given twice daily for 3 days and were initiated at 6, 24, and 48 h after virus inoculation. The gel formulation that contained both 3% foscarnet and 5% SLS and that was administered within 48 h postinfection reduced the rate of development of herpetic skin lesions. This formulation also significantly decreased the viral content in skin tissues and in ipsilateral trigeminal ganglia when it was given within 24 and 6 h postinfection, respectively. A lower level of efficacy was observed for the gel formulation containing 3% foscarnet alone. Of prime interest, the gel formulation containing 5% SLS reduced significantly the mortality rate among mice in a zosteriform model of infection. Both formulations of foscarnet had no effect on the mean titers of reactivated virus in explant cultures of ipsilateral and contralateral trigeminal ganglia from latently infected mice. The use of a gel formulation containing combinations of foscarnet and SLS could represent an attractive approach for the treatment of herpetic mucocutaneous infections. PMID:11257012

  8. 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.

  9. Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1.

    Directory of Open Access Journals (Sweden)

    Natasha Webb

    2008-09-01

    Full Text Available Previous studies have indicated that Epstein-Barr virus (EBV can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1. Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, beta-catenin, Glycogen Synthase Kinase 3ss (GSK3beta, axin and alpha-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and beta-catenin interaction and did not induce transcriptional activation of beta-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1.

  10. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

    Science.gov (United States)

    Deng, Kai; Pertea, Mihaela; Rongvaux, Anthony; Wang, Leyao; Durand, Christine M.; Ghiaur, Gabriel; Lai, Jun; McHugh, Holly L.; Hao, Haiping; Zhang, Hao; Margolick, Joseph B.; Gurer, Cagan; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Deeks, Steven G.; Strowig, Till; Kumar, Priti; Siliciano, Janet D.; Salzberg, Steven L.; Flavell, Richard A.; Shan, Liang; Siliciano, Robert F.

    2015-01-01

    Despite antiretroviral therapy (ART), HIV-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6–8. A key remaining question is whether virus-specific immune mechanisms including cytolytic T lymphocytes (CTL) can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir. PMID:25561180

  11. Chromatin Structure of Epstein-Barr Virus Latent Episomes.

    Science.gov (United States)

    Lieberman, Paul M

    2015-01-01

    EBV latent infection is characterized by a highly restricted pattern of viral gene expression. EBV can establish latent infections in multiple different tissue types with remarkable variation and plasticity in viral transcription and replication. During latency, the viral genome persists as a multi-copy episome, a non-integrated-closed circular DNA with nucleosome structure similar to cellular chromosomes. Chromatin assembly and histone modifications contribute to the regulation of viral gene expression, DNA replication, and episome persistence during latency. This review focuses on how EBV latency is regulated by chromatin and its associated processes.

  12. Epstein-Barr virus infection and nasopharyngeal carcinoma.

    Science.gov (United States)

    Tsao, Sai Wah; Tsang, Chi Man; Lo, Kwok Wai

    2017-10-19

    Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  13. Synthesis of viral DNA forms in Nicotiana plumbaginifolia protoplasts inoculated with cassava latent virus (CLV); evidence for the independent replication of one component of the CLV genome.

    OpenAIRE

    Townsend, R; Watts, J; Stanley, J

    1986-01-01

    Totipotent leaf mesophyll protoplasts of Nicotiana plumbaginifolia, Viviani were inoculated with cassava latent virus (CLV) or with full length copies of CLV genomic DNAs 1 and 2 excised from replicative forms of M13 clones. Virus specific DNAs began to appear 48-72h after inoculation with virus or cloned DNAs, coincident with the onset of host cell division. Infected cells accumulated supercoiled forms of DNAs 1 and 2 as well as progeny single-stranded (ss) virion (+) sense DNAs representing...

  14. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics

    Science.gov (United States)

    Hosmane, Nina N.; Kwon, Kyungyoon J.; Bruner, Katherine M.; Capoferri, Adam A.; Rosenbloom, Daniel I.S.; Keele, Brandon F.; Ho, Ya-Chi

    2017-01-01

    A latent reservoir for HIV-1 in resting CD4+ T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. PMID:28341641

  15. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics.

    Science.gov (United States)

    Hosmane, Nina N; Kwon, Kyungyoon J; Bruner, Katherine M; Capoferri, Adam A; Beg, Subul; Rosenbloom, Daniel I S; Keele, Brandon F; Ho, Ya-Chi; Siliciano, Janet D; Siliciano, Robert F

    2017-04-03

    A latent reservoir for HIV-1 in resting CD4 + T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. © 2017 Hosmane et al.

  16. Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge.

    Science.gov (United States)

    Bolis, Vasileios; Karadedos, Christos; Chiotis, Ioannis; Chaliasos, Nikolaos; Tsabouri, Sophia

    2016-01-01

    Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection. Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation." Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  17. Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment.

    Science.gov (United States)

    Halabi, Mohamad Adnan; Jaccard, Arnaud; Moulinas, Rémi; Bahri, Racha; Al Mouhammad, Hazar; Mammari, Nour; Feuillard, Jean; Ranger-Rogez, Sylvie

    2016-08-15

    Extranodal natural killer/T-cell lymphomas (NK/TL), rare in Europe, are Epstein-Barr virus (EBV) associated lymphomas with poor outcomes. Here, we determined the virus type and analyzed the EBV latent membrane protein-1 (LMP1) gene sequence in NK/TL from French patients. Six clones of viral LMP1 were sequenced by Sanger technology in blood from 13 patients before treatment with an l-asparaginase based regimen and, for 8 of them, throughout the treatment. Blood LMP1 sequences from 21 patients without any known malignancy were tested as controls. EBV Type A was identified for 11/13 patients and for all controls. Before treatment, a clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/TL and only in 4.8% of controls. Treatment was less effective in these patients who died more rapidly than the others. Patients with a deleted strain evolving toward a wild-type strain during treatment reached complete remission. The LMP1 gene was sequenced by highly sensitive next-generation sequencing technology in five NK/TL nasopharyngeal biopsies, two of them originating from the previous patients. Del30 was present in 100% of the biopsies; two viruses at least coexisted in three biopsies. These results suggest that del30 may be associated with poor prognosis NK/TL and that strain evolution could be used as a potential marker to monitor treatment. © 2016 UICC.

  18. Glutamine supplementation suppresses herpes simplex virus reactivation.

    Science.gov (United States)

    Wang, Kening; Hoshino, Yo; Dowdell, Kennichi; Bosch-Marce, Marta; Myers, Timothy G; Sarmiento, Mayra; Pesnicak, Lesley; Krause, Philip R; Cohen, Jeffrey I

    2017-06-30

    Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-γ-inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1-infected IFN-γ-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

  19. Classification criteria of syndromes by latent variable models

    DEFF Research Database (Denmark)

    Petersen, Janne

    2010-01-01

    patient's characteristics. These methods may erroneously reduce multiplicity either by combining markers of different phenotypes or by mixing HALS with other processes such as aging. Latent class models identify homogenous groups of patients based on sets of variables, for example symptoms. As no gold......The thesis has two parts; one clinical part: studying the dimensions of human immunodeficiency virus associated lipodystrophy syndrome (HALS) by latent class models, and a more statistical part: investigating how to predict scores of latent variables so these can be used in subsequent regression...... standard exists for diagnosing HALS the normally applied diagnostic models cannot be used. Latent class models, which have never before been used to diagnose HALS, make it possible, under certain assumptions, to: statistically evaluate the number of phenotypes, test for mixing of HALS with other processes...

  20. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

    Science.gov (United States)

    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  1. Latent variable models are network models.

    Science.gov (United States)

    Molenaar, Peter C M

    2010-06-01

    Cramer et al. present an original and interesting network perspective on comorbidity and contrast this perspective with a more traditional interpretation of comorbidity in terms of latent variable theory. My commentary focuses on the relationship between the two perspectives; that is, it aims to qualify the presumed contrast between interpretations in terms of networks and latent variables.

  2. A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by prunus necrotic ringspot virus and peach latent mosaic viroid.

    Science.gov (United States)

    Herranz, Mari Carmen; Niehl, Annette; Rosales, Marlene; Fiore, Nicola; Zamorano, Alan; Granell, Antonio; Pallas, Vicente

    2013-05-28

    Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in

  3. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    Science.gov (United States)

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  4. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    Science.gov (United States)

    Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

    2016-01-01

    The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  5. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    Directory of Open Access Journals (Sweden)

    Pedro Perdigão

    Full Text Available The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  6. Swine-origin influenza A (H3N2) virus infection in two children--Indiana and Pennsylvania, July-August 2011.

    Science.gov (United States)

    2011-09-09

    Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine. Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission.

  7. Molecular phylogeography of canine distemper virus: Geographic origin and global spreading.

    Science.gov (United States)

    Panzera, Yanina; Sarute, Nicolás; Iraola, Gregorio; Hernández, Martín; Pérez, Ruben

    2015-11-01

    Canine distemper virus (CDV) (Paramyxoviridae-Morbillivirus) is a worldwide spread virus causing a fatal systemic disease in a broad range of carnivore hosts. In this study we performed Bayesian inferences using 208 full-length hemagglutinin gene nucleotide sequences isolated in 16 countries during 37 years (1975-2011). The estimated time to the most recent common ancestor suggested that current CDV strains emerged in the United States in the 1880s. This ancestor diversified through time into two ancestral clades, the current America 1 lineage that recently spread to Asia, and other ancestral clade that diversified and spread worldwide to originate the remaining eight lineages characterized to date. The spreading of CDV was characterized by several migratory events with posterior local differentiation, and expansion of the virus host range. A significant genetic flow between domestic and wildlife hosts is displayed; being domestic hosts the main viral reservoirs worldwide. This study is an extensive and integrative description of spatio/temporal population dynamics of CDV lineages that provides a novel evolutionary paradigm about the origin and dissemination of the current strains of the virus. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Apple latent spherical virus vectors for reliable and effective virus-induced gene silencing among a broad range of plants including tobacco, tomato, Arabidopsis thaliana, cucurbits, and legumes

    International Nuclear Information System (INIS)

    Igarashi, Aki; Yamagata, Kousuke; Sugai, Tomokazu; Takahashi, Yukari; Sugawara, Emiko; Tamura, Akihiro; Yaegashi, Hajime; Yamagishi, Noriko; Takahashi, Tsubasa; Isogai, Masamichi; Takahashi, Hideki; Yoshikawa, Nobuyuki

    2009-01-01

    Apple latent spherical virus (ALSV) vectors were evaluated for virus-induced gene silencing (VIGS) of endogenous genes among a broad range of plant species. ALSV vectors carrying partial sequences of a subunit of magnesium chelatase (SU) and phytoene desaturase (PDS) genes induced highly uniform knockout phenotypes typical of SU and PDS inhibition on model plants such as tobacco and Arabidopsis thaliana, and economically important crops such as tomato, legume, and cucurbit species. The silencing phenotypes persisted throughout plant growth in these plants. In addition, ALSV vectors could be successfully used to silence a meristem gene, proliferating cell nuclear antigen and disease resistant N gene in tobacco and RCY1 gene in A. thaliana. As ALSV infects most host plants symptomlessly and effectively induces stable VIGS for long periods, the ALSV vector is a valuable tool to determine the functions of interested genes among a broad range of plant species.

  9. Reactivation of latent HIV-1 by new semi-synthetic ingenol esters

    Energy Technology Data Exchange (ETDEWEB)

    Pandeló José, Diego [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Bartholomeeusen, Koen [Department of Medicine, Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143-0703 (United States); Delveccio da Cunha, Rodrigo; Abreu, Celina Monteiro [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Glinski, Jan [PlantaAnalytica LLC, Danbury, CT 06810 (United States); Barbizan Ferreira da Costa, Thais; Bacchi Rabay, Ana Flávia Mello; Pianowski Filho, Luiz Francisco [Kyolab Laboratories, Valinhos, São Paulo 13273-105 (Brazil); Dudycz, Lech W. [Lex Company Research Laboratories, Shirley 01464, MA (United States); Ranga, Udaykumar [Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064 (India); Peterlin, Boris Matija [Department of Medicine, Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143-0703 (United States); Pianowski, Luiz Francisco [Kyolab Laboratories, Valinhos, São Paulo 13273-105 (Brazil); Tanuri, Amilcar [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil); Aguiar, Renato Santana, E-mail: santana@biologia.ufrj.br [Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil)

    2014-08-15

    The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus reactivation is dependent on intact NF-κB binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin T1. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART. - Highlights: • 3-caproyl-ingenol (ING B) reactivates latent HIV better than SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. • ING B promotes PKC activation and NF-kB translocation to the nucleus. • ING B activates virus transcription of B and non-B subtypes of HIV-1. • ING B activates HIV transcription in infected primary resting CD4+ T cells. • ING B induces higher levels of P-TEFb components in human primary cells.

  10. Complete nucleotide sequence and genome organization of Olive latent virus 3, a new putative member of the family Tymoviridae.

    Science.gov (United States)

    Alabdullah, Abdulkader; Minafra, Angelantonio; Elbeaino, Toufic; Saponari, Maria; Savino, Vito; Martelli, Giovanni P

    2010-09-01

    The complete nucleotide sequence and the genome organization were determined of a putative new member of the family Tymoviridae, tentatively named Olive latent virus 3 (OLV-3), recovered in southern Italy from a symptomless olive tree. The sequenced ssRNA genome comprises 7148 nucleotides excluding the poly(A) tail and contains four open reading frames (ORFs). ORF1 encodes a polyprotein of 221.6kDa in size, containing the conserved signatures of the methyltransferase (MTR), papain-like protease (PRO), helicase (HEL) and RNA-dependent RNA polymerase (RdRp) domains of the replication-associated proteins of positive-strand RNA viruses. ORF2 overlaps completely ORF1 and encodes a putative protein of 43.33kDa showing limited sequence similarity with the putative movement protein of Maize rayado fino virus (MRFV). ORF3 codes for a protein with predicted molecular mass of 28.46kDa, identified as the coat protein (CP), whereas ORF4 overlaps ORF3 and encodes a putative protein of 16kDa with sequence similarity to the p16 and p31 proteins of Citrus sudden death-associated virus (CSDaV) and Grapevine fleck virus (GFkV), respectively. Within the family Tymoviridae, OLV-3 genome has the closest identity level (49-52%) with members of the genus Marafivirus, from which, however, it differs because of the diverse genome organization and the presence of a single type of CP subunits. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  11. Analysis of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) gene and promoter in Hodgkin's disease isolates

    DEFF Research Database (Denmark)

    Sandvej, K; Andresen, B S; Zhou, X G

    2000-01-01

    AIMS: To study the distribution of Epstein-Barr virus (EBV) variants containing mutations in the latent membrane protein 1 (LMP-1) oncogene and promoter in EBV associated Hodgkin's disease and infectious mononucleosis compared with previous findings in asymptomatic EBV carriers. METHODS: Sequence...... analysis of the EBV LMP-1 promoter and gene in isolates from Danish patients with Hodgkin's disease (n = 61) and infectious mononucleosis (n = 10). RESULTS: Viruses (previously designated group D) that contain two mutations in the activating transcription factor/cAMP response element (ATF/CRE) in the LMP-1...... promoter, which are known to decrease promoter activity greatly, were significantly less frequent in Hodgkin's disease than in both infectious mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In some cases, the LMP-1 gene contained mutations in a recently identified cytotoxic T cell...

  12. Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1

    Science.gov (United States)

    Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Kagaayi, Joseph; Kizza, Allan; Pillay, Visva; Laeyendecker, Oliver; Reynolds, Steven J.; Eshleman, Susan H.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.

    2009-01-01

    Background Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4+ T cells, potentially complicating future treatment. Methods Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4+ T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. PMID:19338474

  13. Occupancy of chromatin organizers in the Epstein-Barr virus genome.

    Science.gov (United States)

    Holdorf, Meghan M; Cooper, Samantha B; Yamamoto, Keith R; Miranda, J J L

    2011-06-20

    The human CCCTC-binding factor, CTCF, regulates transcription of the double-stranded DNA genomes of herpesviruses. The architectural complex cohesin and RNA Polymerase II also contribute to this organization. We profiled the occupancy of CTCF, cohesin, and RNA Polymerase II on the episomal genome of the Epstein-Barr virus in a cell culture model of latent infection. CTCF colocalizes with cohesin but not RNA Polymerase II. CTCF and cohesin bind specific sequences throughout the genome that are found not just proximal to the regulatory elements of latent genes, but also near lytic genes. In addition to tracking with known transcripts, RNA Polymerase II appears at two unannotated positions, one of which lies within the latent origin of replication. The widespread occupancy profile of each protein reveals binding near or at a myriad of regulatory elements and suggests context-dependent functions. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV.

    Science.gov (United States)

    Kim, Youry; Anderson, Jenny L; Lewin, Sharon R

    2018-01-10

    Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival. Here, we review new approaches to induce death of latently infected cells through apoptosis and inhibition of pathways critical for cell survival, which are often hijacked by HIV proteins. Given advances in the commercial development of compounds that induce apoptosis in cancer chemotherapy, these agents could move rapidly into clinical trials, either alone or in combination with LRAs, to eliminate latent HIV infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

    Science.gov (United States)

    Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

    2011-01-01

    Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

  16. Homeostatic proliferation fails to efficiently reactivate HIV-1 latently infected central memory CD4+ T cells.

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    Alberto Bosque

    2011-10-01

    Full Text Available Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.

  17. Infection cycle of Artichoke Italian latent virus in tobacco plants: meristem invasion and recovery from disease symptoms.

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    Elisa Santovito

    Full Text Available Nepoviral infections induce recovery in fully expanded leaves but persist in shoot apical meristem (SAM by a largely unknown mechanism. The dynamics of infection of a grapevine isolate of Artichoke Italian latent virus (AILV-V, genus Nepovirus in tobacco plants, including colonization of SAM, symptom induction and subsequent recovery of mature leaves from symptoms, were characterized. AILV-V moved from the inoculated leaves systemically and invaded SAM in 7 days post-inoculation (dpi, remaining detectable in SAM at least up to 40 dpi. The new top leaves recovered from viral symptoms earliest at 21 dpi. Accumulation of viral RNA to a threshold level was required to trigger the overexpression of RDR6 and DCL4. Consequently, accumulation of viral RNA decreased in the systemically infected leaves, reaching the lowest concentration in the 3rd and 4th leaves at 23 dpi, which was concomitant with recovery of the younger, upper leaves from disease symptoms. No evidence of virus replication was found in the recovered leaves, but they contained infectious virus particles and were protected against re-inoculation with AILV-V. In this study we also showed that AILV-V did not suppress initiation or maintenance of RNA silencing in transgenic plants, but was able to interfere with the cell-to-cell movement of the RNA silencing signal. Our results suggest that AILV-V entrance in SAM and activation of RNA silencing may be distinct processes since the latter is triggered in fully expanded leaves by the accumulation of viral RNA above a threshold level rather than by virus entrance in SAM.

  18. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay.

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    Gregory M Laird

    Full Text Available HIV-1 persists in infected individuals in a stable pool of resting CD4(+ T cells as a latent but replication-competent provirus. This latent reservoir is the major barrier to the eradication of HIV-1. Clinical trials are currently underway investigating the effects of latency-disrupting compounds on the persistence of the latent reservoir in infected individuals. To accurately assess the effects of such compounds, accurate assays to measure the frequency of latently infected cells are essential. The development of a simpler assay for the latent reservoir has been identified as a major AIDS research priority. We report here the development and validation of a rapid viral outgrowth assay that quantifies the frequency of cells that can release replication-competent virus following cellular activation. This new assay utilizes bead and column-based purification of resting CD4(+ T cells from the peripheral blood of HIV-1 infected patients rather than cell sorting to obtain comparable resting CD4(+ T cell purity. This new assay also utilizes the MOLT-4/CCR5 cell line for viral expansion, producing statistically comparable measurements of the frequency of latent HIV-1 infection. Finally, this new assay employs a novel quantitative RT-PCR specific for polyadenylated HIV-1 RNA for virus detection, which we demonstrate is a more sensitive and cost-effective method to detect HIV-1 replication than expensive commercial ELISA detection methods. The reductions in both labor and cost make this assay suitable for quantifying the frequency of latently infected cells in clinical trials of HIV-1 eradication strategies.

  19. Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription.

    Science.gov (United States)

    Khalil, Mohamed I; Sommer, Marvin H; Hay, John; Ruyechan, William T; Arvin, Ann M

    2015-07-01

    The VZV genome has two origins of DNA replication (oriS), each of which consists of an AT-rich sequence and three origin binding protein (OBP) sites called Box A, C and B. In these experiments, the mutation in the core sequence CGC of the Box A and C not only inhibited DNA replication but also inhibited both ORF62 and ORF63 expression in reporter gene assays. In contrast the Box B mutation did not influence DNA replication or flanking gene transcription. These results suggest that efficient DNA replication enhances ORF62 and ORF63 transcription. Recombinant viruses carrying these mutations in both sites and one with a deletion of the whole oriS were constructed. Surprisingly, the recombinant virus lacking both copies of oriS retained the capacity to replicate in melanoma and HELF cells suggesting that VZV has another origin of DNA replication. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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. A Taxonomy of Latent Structure Assumptions for Probability Matrix Decomposition Models.

    Science.gov (United States)

    Meulders, Michel; De Boeck, Paul; Van Mechelen, Iven

    2003-01-01

    Proposed a taxonomy of latent structure assumptions for probability matrix decomposition (PMD) that includes the original PMD model and a three-way extension of the multiple classification latent class model. Simulation study results show the usefulness of the taxonomy. (SLD)

  2. Characterization of viruses associated with garlic plants propagated from different reproductive tissues from Italy and other geographic regions

    Directory of Open Access Journals (Sweden)

    Leonardo PARRANO

    2013-01-01

    Full Text Available Garlic is an important crop cultivated worldwide and several different viruses have been associated with propagative material. Garlic is propagated from bulbs and/or from vegetative topsets of the inflorescences known as bulbils. The effects of the geographic origin and the type of the propagative material on the phylogenetic relationships and genetic variability of the coat protein genes of four allium viruses are presented here. Onion yellow dwarf virus (OYDV, Leek yellow stripe virus (LYSV, Garlic virus X (GVX, and Garlic common latent virus (GCLV were detected in single and mixed infections in plants grown either from bulbils and/or bulbs originating from Italy, China, Argentina, and the U.S.A. OYDV and LYSV fell into five and three well supported clades respectively whereas isolates of GVX and GCLV all clustered into one well-supported clade each. Some of the OYDV and LYSV clades presented evidence of host tissue selection while some phylogenetic structuring based on the geographic origin or host was also observed for some virus clades. Unique haplotypes and novel coat protein amino acid sequence patterns were identified for all viruses. An OYDV coat protein amino acid signature unique to Chenopodium quinoa, an uncommon host of the virus, was of particular interest. The type of propagative material affected the population dynamics of all of the viruses. The virus populations in plants propagated from bulbs were more diverse than in plants propagated from bulbils.

  3. A novel Cre recombinase imaging system for tracking lymphotropic virus infection in vivo.

    Directory of Open Access Journals (Sweden)

    Bernadette M Dutia

    2009-08-01

    Full Text Available Detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. However, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. We have designed a novel Cre recombinase (Cre-based murine system to overcome these problems, and thereby enable tracking and isolation of individual in vivo infected cells.Murine gammaherpesvirus 68 (MHV-68 was used as a prototypic persistent model virus. A Cre expressing recombinant virus was constructed and characterised. The virus is attenuated both in lytic virus replication, producing ten-fold lower lung virus titres than wild type virus, and in the establishment of latency. However, despite this limitation, when the sEGFP7 mouse line containing a Cre-activated enhanced green fluorescent protein (EGFP was infected with the Cre expressing virus, sites of latent and persistent virus infection could be identified within B cells and macrophages of the lymphoid system on the basis of EGFP expression. Importantly, the use of the sEGFP7 mouse line which expresses high levels of EGFP allowed individual virus positive cells to be purified by FACSorting. Virus gene expression could be detected in these cells. Low numbers of EGFP positive cells could also be detected in the bone marrow.The use of this novel Cre-based virus/mouse system allowed identification of individual latently infected cells in vivo and may be useful for the study and long-term monitoring of other latent/persistent virus infections.

  4. Latent potyvirus infections in Crocus sativus artwrightianus: an underestimated problem in saffron?

    Directory of Open Access Journals (Sweden)

    Maria GRILLI CAIOLA

    2011-09-01

    Full Text Available Normal 0 14 false false false IT X-NONE X-NONE MicrosoftInternetExplorer4 In over two decades, while studying saffron reproductive biology, we frequently found ultrastructural alterations typical of potyvirus infection in stigmas, styles and leaves of Crocus sativus (saffron and C. cartwrightianus (wild and ornamental species, a putative ancestor of saffron from different provenance. This suggests that these viruses are widely diffused in cultivated Crocus spp., possibly causing latent infections. The few data found in literature, while highlighting the general lack of attention given by plant virologists to Crocus spp., nevertheless confi rm that potyviruses, particularly Bean yellow mosaic virus (BYMV, can cause asymptomatic infections in these host species. The reasons and possible implications of widely distributed potyvirus latent infections in Crocus spp. are reported and discussed, with the aim of increasing general awareness of these viruses, and of encouraging sanitary selection programs focused on saffron, that could improve the quantity and quality of yields of the most expensive spice commodity grown.

  5. Das Epstein-Barr-Virus ( = Epstein-Barr virus)

    OpenAIRE

    Niller, H. H.; Wolf, Hans J.

    1993-01-01

    Epstein-Barr virus is an ubiquitous humanpathogenic herpesvirus. It has been identified as the etiologic agent of infectious mononucleosis. In addition it is associated with the cancers nasopharyngeal carcinoma and Burkitt's lymphoma. Like other herpesviruses it infects cells in a lytic way or it persists in a latent state. Classically, the serologic diagnosis of Epstein-Barr virus infections is done by the agglutination of sheep erythrocytes according to Paul and Bunnell as a rapid testing m...

  6. General properties of grapevine viruses occurring in Hungary

    OpenAIRE

    Eszter Cseh; András Takács; László Kocsis; Richard Gáborjányi

    2012-01-01

    The past fifty years important advances have been made in the field of grapevine virus research, including characterization of pathogens and control measurements. Still the occurrence of Grapevine fanleaf virus (GFLV), Arabis mosaic virus (ArMV), Tomato black ring virus (TBRV), Grapevine chrome mosaic virus (GCMV), Alfalfa mosaic virus (AMV), Grapevine Bulgarian latent virus (GBLV), Grapevine fleck virus (GFkV), Grapevine leafroll- associated viruses (GLRaV1-4), Grapevine virus A (GVA), Grape...

  7. Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner.

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    Rajeev Mehla

    2010-06-01

    Full Text Available HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC -alpha and -delta, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC involving stress induced AMP Kinase (AMPK inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs.

  8. The Origin of the Variola Virus

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    Igor V. Babkin

    2015-03-01

    Full Text Available The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV, which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts’ ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10−6 substitutions/site/year for the central conserved genomic region and 4 × 10−6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.

  9. An in-depth analysis of original antigenic sin in dengue virus infection.

    Science.gov (United States)

    Midgley, Claire M; Bajwa-Joseph, Martha; Vasanawathana, Sirijitt; Limpitikul, Wannee; Wills, Bridget; Flanagan, Aleksandra; Waiyaiya, Emily; Tran, Hai Bac; Cowper, Alison E; Chotiyarnwong, Pojchong; Chotiyarnwon, Pojchong; Grimes, Jonathan M; Yoksan, Sutee; Malasit, Prida; Simmons, Cameron P; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2011-01-01

    The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.

  10. Usage of Latent Class Analysis in Diagnostic Microbiology in the Absence of Gold Standard Test

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    Gul Bayram Abiha

    2016-12-01

    Full Text Available The evaluation of performance of various tests diagnostic tests in the absence of gold standard is an important problem. Latent class analysis (LCA is a statistical analysis method known for many years, especially in the absence of a gold standard for evaluation of diagnostic tests so that LCA has found its wide application area. During the last decade, LCA method has widely used in for determining sensivity and specifity of different microbiological tests. It has investigated in the diagnosis of mycobacterium tuberculosis, mycobacterium bovis, human papilloma virus, bordetella pertussis, influenza viruses, hepatitis E virus (HEV, hepatitis C virus (HCV and other various viral infections. Researchers have compared several diagnostic tests for the diagnosis of different pathogens with LCA. We aimed to evaluate performance of latent class analysis method used microbiological diagnosis in various diseases in several researches. When we took into account all of these tests' results, we suppose that LCA is a good statistical analysis method to assess different test performances in the absence of gold standard. [Archives Medical Review Journal 2016; 25(4.000: 467-488

  11. Modulation of the tumor microenvironment by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yoshizaki, Tomokazu; Kondo, Satoru; Endo, Kazuhira; Nakanishi, Yosuke; Aga, Mitsuharu; Kobayashi, Eiji; Hirai, Nobuyuki; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Wakisaka, Naohiro

    2018-02-01

    Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but it still has a pivotal role during all stages of NPC development. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Diversity and origin of hepatitis B virus in Dutch blood donors

    NARCIS (Netherlands)

    Koppelman, M. H. G. M.; Zaaijer, H. L.

    2004-01-01

    Two considerations led us to study the genetic diversity and origin of hepatitis B virus (HBV) in Dutch blood donors. Firstly, an HBV-infected Dutch blood donor was found negative by four assays used commonly for detection of HBV surface antigen (HBsAg). How variable is HBsAg among HBV infected

  13. Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

    2016-03-01

    A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

  14. Epstein-Barr Virus Lymphoproliferative Disease Following Allogeneic Hematopoietic Stem Cell Transplantation: Prediction and Early Intervention

    NARCIS (Netherlands)

    J.W.J. van Esser (Joost)

    2003-01-01

    textabstractEpstein-Barr virus (EBV) has been associated with a variety of both infectious and malignant human diseases. These viruses are characterized by (B-cell) lymphotropism, their ability to establish latent infection in host cells and to induce proliferation of these latently infected cells.

  15. Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection.

    Science.gov (United States)

    Perry, Clarice L; Banasik, Brianne N; Gorder, Summer R; Xia, Jingya; Auclair, Sarah; Bourne, Nigel; Milligan, Gregg N

    2016-12-01

    Genital infections with herpes simplex virus type 2 (HSV-2) are a source of considerable morbidity and are a health concern for newborns exposed to virus during vaginal delivery. Additionally, HSV-2 infection diminishes the integrity of the vaginal epithelium resulting in increased susceptibility of individuals to infection with other sexually transmitted pathogens. Understanding immune protection against HSV-2 primary infection and immune modulation of virus shedding events following reactivation of the virus from latency is important for the development of effective prophylactic and therapeutic vaccines. Although the murine model of HSV-2 infection is useful for understanding immunity following immunization, it is limited by the lack of spontaneous reactivation of HSV-2 from latency. Genital infection of guinea pigs with HSV-2 accurately models the disease of humans including the spontaneous reactivation of HSV-2 from latency and provides a unique opportunity to examine virus-host interactions during latency. Although the guinea pig represents an accurate model of many human infections, relatively few reagents are available to study the immunological response to infection. To analyze the cell-mediated immune response of guinea pigs at extended periods of time after establishment of HSV-2 latency, we have modified flow-cytometry based proliferation assays and IFN-γ ELISPOT assays to detect and quantify HSV-specific cell-mediated responses during latent infection of guinea pigs. Here we demonstrate that a combination of proliferation and ELISPOT assays can be used to quantify and characterize effecter function of virus-specific immune memory responses during HSV-latency. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

    Science.gov (United States)

    Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

    2014-11-01

    Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our

  17. High similarity between isolates of pepino mosaic virus suggests a common origin

    NARCIS (Netherlands)

    Verhoeven, J.Th.J.; Vlugt, van der R.A.A.; Roenhorst, J.W.

    2003-01-01

    The almost simultaneous outbreaks of Pepino mosaic virus in tomato crops in different European and non-European countries, was reason to have a closer look at the relationship between these isolates and the original isolate from pepino. Fifteen isolates from tomato from different locations and the

  18. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.

    2011-01-01

    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the up......Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...... and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig...

  19. A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

    Directory of Open Access Journals (Sweden)

    Sara Campos da Silva

    2011-05-01

    Full Text Available Mutant viral strains deleted in non-essential genes represent useful tools to study the function of specific gene products in the biology of the virus. We herein describe an investigation on the phenotype of a bovine herpesvirus 5 (BoHV-5 recombinant deleted in the gene encoding the enzyme thymidine kinase (TK in rabbits, with special emphasis to neuroinvasiveness and the ability to establish and reactivate latent infection. Rabbits inoculated with the parental virus (SV-507/99 (n=18 at a low titer (10(5.5TCID50 shed virus in nasal secretions in titers up to 10(4.5TCID50 for up to 12 days (average: 9.8 days [5-12] and 5/ 16 developed neurological disease and were euthanized in extremis. Rabbits inoculated with the recombinant BoHV-5TKΔ at a high dose (10(7.1TCID50 also shed virus in nasal secretions, yet to lower titers (maximum: 10(2.3TCID50 and for a shorter period (average: 6.6 days [2-11] and remained healthy. PCR examination of brain sections of inoculated rabbits at day 6 post-infection (pi revealed a widespread distribution of the parental virus, whereas DNA of the recombinant BoHV-5TKΔ-was detected only in the trigeminal ganglia [TG] and olfactory bulbs [OB]. Nevertheless, during latent infection (52pi, DNA of the recombinant virus was detected in the TGs, OBs and also in other areas of the brain, demonstrating the ability of the virus to invade the brain. Dexamethasone (Dx administration at day 65 pi was followed by virus reactivation and shedding by 5/8 rabbits inoculated with the parental strain (mean duration of 4.2 days [1 - 9] and by none of seven rabbits inoculated with the recombinant virus. Again, PCR examination at day 30 post-Dx treatment revealed the presence of latent DNA in the TGs, OBs and in other areas of the brain of both groups. Taken together, these results confirm that the recombinant BoHV-5TKΔ is highly attenuated for rabbits. It shows a reduced ability to replicate in the nose but retains the ability to invade

  20. Molecular characterisation of the full-length genome of olive latent virus 1 isolated from tomato.

    Science.gov (United States)

    Hasiów-Jaroszewska, Beata; Borodynko, Natasza; Pospieszny, Henryk

    2011-05-01

    Olive latent virus 1 (OLV-1) is a species of the Necrovirus genus. So far, it has been reported to infect olive, citrus tree and tulip. Here, we determined and analysed the complete genomic sequence of an isolate designated as CM1, which was collected from tomato plant in the Wielkopolska region of Poland and represents the prevalent isolate of OLV-1. The CM1 genome consists of monopartite single-stranded positive-sense RNA genome sized 3,699 nt with five open reading frames (ORFs) and small inter-cistronic regions. ORF1 encodes a polypeptide with a molecular weight of 23 kDa and the read-through (RT) of its amber stop codon results in ORF1 RT that encodes the virus RNA-dependent RNA polymerase. ORF2 and ORF3 encode two peptides, with 8 kDa and 6 kDa, respectively, which appear to be involved in cell-to-cell movement. ORF4 is located in the 3' terminal and encodes a protein with 30 kDa identified as the viral coat protein (CP). The differences in CP region of four OLV-1 isolates whose sequences have been deposited in GenBank were observed. Nucleotide sequence identities of the CP of tomato CM1 isolate with those of olive, citrus and tulip isolates were 91.8%, 89.5% and 92.5%, respectively. In contrast to other OLV-1 isolates, CM1 induced necrotic spots on tomato plants and elicited necrotic local lesions on Nicotiana benthamiana, followed by systemic infection. This is the third complete genomic sequence of OLV-1 reported and the first one from tomato.

  1. Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses

    OpenAIRE

    Dybing, Jody K.; Schultz-Cherry, Stacey; Swayne, David E.; Suarez, David L.; Perdue, Michael L.

    2000-01-01

    In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian in...

  2. Apple Latent Spherical Virus Vector as Vaccine for the Prevention and Treatment of Mosaic Diseases in Pea, Broad Bean, and Eustoma Plants by Bean Yellow Mosaic Virus

    Directory of Open Access Journals (Sweden)

    Nozomi Satoh

    2014-11-01

    Full Text Available We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV harboring a segment of the Bean yellow mosaic virus (BYMV genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge inoculated with BYMV expressing green fluorescence protein, BYMV multiplication occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No mosaic symptoms due to BYMV infection were observed in the challenged plants pre-inoculated with the ALSV vaccine. Simultaneous inoculation with the ALSV vaccine and BYMV also prevented mosaic symptoms in broad bean and eustoma plants, and BYMV accumulation was strongly inhibited in the upper leaves of plants treated with the ALSV vaccine. Pea and eustoma plants were pre-inoculated with BYMV followed by inoculation with the ALSV vaccine to investigate the curative effects of the ALSV vaccine. In both plant species, recovery from mosaic symptoms was observed in upper leaves and BYMV accumulation was inhibited in leaves developing post-ALSV vaccination. These results show that ALSV vaccination not only prevents mosaic diseases in pea, broad bean, and eustoma, but that it is also effective in curing these diseases.

  3. Herpes simplex virus following stab phlebectomy.

    Science.gov (United States)

    Hicks, Caitlin W; Lum, Ying Wei; Heller, Jennifer A

    2017-03-01

    Herpes simplex virus infection following surgery is an unusual postoperative phenomenon. Many mechanisms have been suggested, with the most likely explanation related to latent virus reactivation due to a proinflammatory response in the setting of local trauma. Here, we present a case of herpes simplex virus reactivation in an immunocompetent female following a conventional right lower extremity stab phlebectomy. Salient clinical and physical examination findings are described, and management strategies for herpes simplex virus reactivation are outlined. This is the first known case report of herpes simplex virus reactivation following lower extremity phlebectomy.

  4. Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases.

    Science.gov (United States)

    Wu, Zhiqiang; Yang, Li; Ren, Xianwen; He, Guimei; Zhang, Junpeng; Yang, Jian; Qian, Zhaohui; Dong, Jie; Sun, Lilian; Zhu, Yafang; Du, Jiang; Yang, Fan; Zhang, Shuyi; Jin, Qi

    2016-03-01

    Studies have demonstrated that ~60%-80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.

  5. Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

    Science.gov (United States)

    Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

    2017-03-01

    Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Ridge Width Correlations between Inked Prints and Powdered Latent Fingerprints.

    Science.gov (United States)

    De Alcaraz-Fossoul, Josep; Barrot-Feixat, Carme; Zapico, Sara C; Mancenido, Michelle; Broatch, Jennifer; Roberts, Katherine A; Carreras-Marin, Clara; Tasker, Jack

    2017-10-03

    A methodology to estimate the time of latent fingerprint deposition would be of great value to law enforcement and courts. It has been observed that ridge topography changes as latent prints age, including the widths of ridges that could be measured as a function of time. Crime suspects are commonly identified using fingerprint databases that contain reference inked tenprints (flat and rolled impressions). These can be of interest in aging studies as they provide baseline information relating to the original (nonaged) ridges' widths. In practice, the age of latent fingerprints could be estimated following a comparison process between the evidentiary aged print and the corresponding reference inked print. The present article explores possible correlations between inked and fresh latent fingerprints deposited on different substrates and visualized with TiO 2 . The results indicate that the ridge width of flat inked prints is most similar to fresh latent fingerprints , and these should be used as the comparison standard for future aging studies. © 2017 American Academy of Forensic Sciences.

  7. Induction and maintenance of DNA methylation in plant promoter sequences by apple latent spherical virus-induced transcriptional gene silencing

    Directory of Open Access Journals (Sweden)

    Tatsuya eKon

    2014-11-01

    Full Text Available Apple latent spherical virus (ALSV is an efficient virus-induced gene silencing vector in functional genomics analyses of a broad range of plant species. Here, an Agrobacterium-mediated inoculation (agroinoculation system was developed for the ALSV vector, and virus-induced transcriptional gene silencing (VITGS is described in plants infected with the ALSV vector. The cDNAs of ALSV RNA1 and RNA2 were inserted between the CaMV 35S promoter and the NOS-T sequences in a binary vector pCAMBIA1300 to produce pCALSR1 and pCALSR2-XSB or pCALSR2-XSB/MN. When these vector constructs were agroinoculated into Nicotiana benthamiana plants with a construct expressing a viral silencing suppressor, the infection efficiency of the vectors was 100%. A recombinant ALSV vector carrying part of the 35S promoter sequence induced transcriptional gene silencing of the green fluorescent protein gene in a line of N. benthamiana plants, resulting in the disappearance of green fluorescence of infected plants. Bisulfite sequencing showed that cytosine residues at CG and CHG sites of the 35S promoter sequence were highly methylated in the silenced generation 0 plants infected with the ALSV carrying the promoter sequence as well as in progeny. The ALSV-mediated VITGS state was inherited by progeny for multiple generations. In addition, induction of VITGS of an endogenous gene (chalcone synthase-A was demonstrated in petunia plants infected with an ALSV vector carrying the native promoter sequence. These results suggest that ALSV-based vectors can be applied to study DNA methylation in plant genomes, and provide a useful tool for plant breeding via epigenetic modification.

  8. c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

    Science.gov (United States)

    Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

    2018-01-15

    Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

  9. Cell-mediated immunity in herpes simplex virus-infected mice: functional analysis of lymph node cells during periods of acute and latent infection, with reference to cytotoxic and memory cells.

    Science.gov (United States)

    Nash, A A; Quartey-Papafio, R; Wildy, P

    1980-08-01

    The functional characteristics of lymphoid cells were investigated during acute and latent infection of mice with herpes simplex virus (HSV). Cytotoxic T cells were found in the draining lymph node (DLN) 4 days p.i. and had reached maximum activity between 6 and 9 days. After the 12th day and during the period of latent infection (> 20 days) no cytotoxic cell activity was observed. Cytotoxic activity could only be detected when the lymphoid cells had been cultured for a period of 3 days. In general, the cell killing was specific for syngeneic infected target cells, although some killing of uninfected targets was observed. In contrast to the cytotoxic response, DLN cells responding to HSV in a proliferation assay were detected towards the end of the acute phase and at lease up to 9 months thereafter. The significance of these observations for the pathogenesis of HSV is discussed.

  10. Acute and latent infection by bovine herpesvirus type 2 in a guinea pig model.

    Science.gov (United States)

    Torres, Fabrício Dias; Cargnelutti, Juliana Felipetto; Masuda, Eduardo Kenji; Weiblen, Rudi; Flores, Eduardo Furtado

    2010-02-01

    Bovine herpetic mammillits is a self-limiting cutaneous disease of the udder and teats of cows associated with bovine herpesvirus 2 (BoHV-2) whose pathogenesis is poorly understood. This article describes the use of guinea pigs (Cavia porcellus) to study the pathogenesis of BoHV-2 infection. Twelve weanling female guinea pigs inoculated subcutaneously with BoHV-2 in the genitalia and teats developed local hyperemia, edema, vesicles, ulcers and scabs. Infectious virus was recovered between days 3 and 7 post-infection (pi) from the genital area (9/12) and teats (1/12); and all inoculated animals seroconverted (virus-neutralizing titers of 16-128). Histological examination of lesions revealed lymphoplasmacytic perivascular infiltrates and intranuclear inclusion bodies in keratinocytes. PCR examination of tissues collected at day 35 pi detected latent viral DNA predominantly in lumbosacral spinal segments. In another experiment, eight females inoculated with BoHV-2 in the genitalia and treated with dexamethasone (Dx) at day 35 pi developed mild to moderate local signs, yet no virus could be recovered from lesions. PCR examination of spinal segments from these animals confirmed the presence of latent viral DNA. These results demonstrate that guinea pigs are susceptible to BoHV-2 infection and therefore may be used to study selected aspects of BoHV-2 biology.

  11. Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1.

    Science.gov (United States)

    Wang, Qianli; Lingel, Amy; Geiser, Vicki; Kwapnoski, Zachary; Zhang, Luwen

    2017-10-15

    Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and

  12. THE MOLECULAR MECHANISMS OF EPSTEINBARR VIRUS PERSISTENCE IN THE HUMAN ORGANISM

    Directory of Open Access Journals (Sweden)

    Volyanskiy A.Yu.

    2014-12-01

    Full Text Available This review describes advances in molecular aspects of EBV infection and disease. We discuss the spectrum of clinical illness due to EBV persistent infection. The main characteristic of Epstein-Barr virus (EBV is that initial infection results in lifelong persistence. EBV infects nearly all humans by the time they reach adulthood. Healthy humans have approximately 1 to 50 infected cells per million leukocytes. EBV is one of the eight known human herpesviruses. EBV virions have a doublestranded linear DNA and 100 genes had been described in virus genome. Initial infection is thought to occur in the oral compartment. The host cells of EBV are mainly lymphocytes and epithelial cells. EBV attaches to B cells via binding of the viral gp350 protein to CD21 receptor. The consequence of EBV infection is cells proliferation and differentiation into memory B lymphocyte in the germinal center. Infected memory B cells are released into the peripheral circulation. EBV persists mostly in the memory B cell. Latency is the state of persistent viral infection without active viral production. In latently infected B cells EBV virus exist as episomes. During the latent phase episomal replication occurs via host DNA polymerase. Genes of the nuclear antigens (EBNA and latent membrane proteins (LMP are transcribed during latency. These include EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, EBNA leader protein (EBNALP, LMP1 and LMP2 genes. All nuclear antigens are transcription transactivators which bind to cis-regulatory DNA elements of cell or virus genomes directly or in complex with other proteins. LMP2A and LMP1 can function to coordinately mimic B-cell receptor and CD40 coreceptor signaling in latently infected B cells. LMP proteins activate cell signaling systems and as the consequence different gene expression programs. Characterization of gene expression patterns in different cell lines and pathologic conditions has revealed that there are at least three different

  13. Latent heat coldness storage; Stockage du froid par chaleur latente

    Energy Technology Data Exchange (ETDEWEB)

    Dumas, J.P. [Pau Univ., Lab. de Thermodynamique et Energetique, LTE, 64 (France)

    2002-07-01

    This article presents the advantages of latent heat storage systems which use the solid-liquid phase transformation of a pure substance or of a solution. The three main methods of latent heat storage of coldness are presented: ice boxes, encapsulated nodules, and ice flows: 1 - definition of the thermal energy storage (sensible heat, latent heat, thermochemical storage); 2 - advantages and drawbacks of latent heat storage; 3 - choice criteria for a phase-change material; 4 - phenomenological aspect of liquid-solid transformations (phase equilibrium, crystallisation and surfusion); 5 - different latent heat storage processes (ice boxes, encapsulated nodules, two-phase refrigerating fluids); 6 - ice boxes (internal and external melting, loop, air injection, measurement of ice thickness); 7 - encapsulated nodules (nodules, tank, drainage, advantage and drawbacks, charge and discharge); 8 - two-phase refrigerating fluids (composition, ice fabrication, flow circulation, flow storage, exchangers). (J.S.)

  14. Sequencing and phylogenetic analysis of Herpes simplex virus type ...

    African Journals Online (AJOL)

    momtaz

    2012-01-19

    Jan 19, 2012 ... Herpes simplex virus type 2 (HSV-2) is the main cause of recurrent genital infection (Slomka, 1996). Most infections are asymptomatic. The virus establishes latent infection in the local ganglia and is reactivated and shed frequently. Antibodies to HSV infections become detectable in serum samples (Koelle ...

  15. Simultaneous detection of four garlic viruses by multiplex reverse transcription PCR and their distribution in Indian garlic accessions.

    Science.gov (United States)

    Majumder, S; Baranwal, V K

    2014-06-01

    Indian garlic is infected with Onion yellow dwarf virus (OYDV), Shallot latent virus (SLV), Garlic common latent virus (GarCLV) and allexiviruses. Identity and distribution of garlic viruses in various garlic accessions from different geographical regions of India were investigated. OYDV and allexiviruses were observed in all the garlic accessions, while SLV and GarCLV were observed only in a few accessions. A multiplex reverse transcription (RT)-PCR method was developed for the simultaneous detection and identification of OYDV, SLV, GarCLV and Allexivirus infecting garlic accessions in India. This multiplex protocol standardized in this study will be useful in indexing of garlic viruses and production of virus free seed material. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Complete nucleotide sequence of watermelon chlorotic stunt virus originating from Oman.

    Science.gov (United States)

    Khan, Akhtar J; Akhtar, Sohail; Briddon, Rob W; Ammara, Um; Al-Matrooshi, Abdulrahman M; Mansoor, Shahid

    2012-07-01

    Watermelon chlorotic stunt virus (WmCSV) is a bipartite begomovirus (genus Begomovirus, family Geminiviridae) that causes economic losses to cucurbits, particularly watermelon, across the Middle East and North Africa. Recently squash (Cucurbita moschata) grown in an experimental field in Oman was found to display symptoms such as leaf curling, yellowing and stunting, typical of a begomovirus infection. Sequence analysis of the virus isolated from squash showed 97.6-99.9% nucleotide sequence identity to previously described WmCSV isolates for the DNA A component and 93-98% identity for the DNA B component. Agrobacterium-mediated inoculation to Nicotiana benthamiana resulted in the development of symptoms fifteen days post inoculation. This is the first bipartite begomovirus identified in Oman. Overall the Oman isolate showed the highest levels of sequence identity to a WmCSV isolate originating from Iran, which was confirmed by phylogenetic analysis. This suggests that WmCSV present in Oman has been introduced from Iran. The significance of this finding is discussed.

  17. Origin of envelope proteins of a leukemia virus

    International Nuclear Information System (INIS)

    Schneider, R.P.

    1975-01-01

    The roles of avian myeloblastosis virus (AMV) and host myeloblast cells in controlling the protein composition of virus envelope and host cell membrane are being studied by examining an ATPase enzyme in the virus and cells. New culture techniques for virus producing myeloblasts have been developed. (U.S.)

  18. Prevalence of latent alpha-herpesviruses in Thoroughbred racing horses.

    Science.gov (United States)

    Pusterla, Nicola; Mapes, Samantha; David Wilson, W

    2012-08-01

    The objective of this study was to detect and characterize latent equine herpes virus (EHV)-1 and -4 from the submandibular (SMLN) and bronchial lymph (BLN) nodes, as well as from the trigeminal ganglia (TG) of 70 racing Thoroughbred horses submitted for necropsy following sustaining serious musculoskeletal injuries while racing. A combination of nucleic acid precipitation and pre-amplification steps was used to increase analytical sensitivity. Tissues were deemed positive for latent EHV-1 and/or -4 infection when found PCR positive for the corresponding glycoprotein B (gB) gene in the absence of detectable late structural protein gene (gB gene) mRNA. The EHV-1 genotype was also determined using a discriminatory real-time PCR assay targeting the DNA polymerase gene (ORF 30). Eighteen (25.7%) and 58 (82.8%) horses were PCR positive for the gB gene of EHV-1 and -4, respectively, in at least one of the three tissues sampled. Twelve horses were dually infected with EHV-1 and -4, two carried a latent neurotropic strain of EHV-1, six carried a non-neurotropic genotype of EHV-1 and 10 were dually infected with neurotropic and non-neurotropic EHV-1. The distribution of latent EHV-1 and -4 infection varied in the samples, with the TG found to be most commonly infected. Overall, non-neurotropic strains were more frequently detected than neurotropic strains, supporting the general consensus that non-neurotropic strains are more prevalent in horse populations, and hence the uncommon occurrence of equine herpes myeloencephalopathy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Latent palmprint matching.

    Science.gov (United States)

    Jain, Anil K; Feng, Jianjiang

    2009-06-01

    The evidential value of palmprints in forensic applications is clear as about 30 percent of the latents recovered from crime scenes are from palms. While biometric systems for palmprint-based personal authentication in access control type of applications have been developed, they mostly deal with low-resolution (about 100 ppi) palmprints and only perform full-to-full palmprint matching. We propose a latent-to-full palmprint matching system that is needed in forensic applications. Our system deals with palmprints captured at 500 ppi (the current standard in forensic applications) or higher resolution and uses minutiae as features to be compatible with the methodology used by latent experts. Latent palmprint matching is a challenging problem because latent prints lifted at crime scenes are of poor image quality, cover only a small area of the palm, and have a complex background. Other difficulties include a large number of minutiae in full prints (about 10 times as many as fingerprints), and the presence of many creases in latents and full prints. A robust algorithm to reliably estimate the local ridge direction and frequency in palmprints is developed. This facilitates the extraction of ridge and minutiae features even in poor quality palmprints. A fixed-length minutia descriptor, MinutiaCode, is utilized to capture distinctive information around each minutia and an alignment-based minutiae matching algorithm is used to match two palmprints. Two sets of partial palmprints (150 live-scan partial palmprints and 100 latent palmprints) are matched to a background database of 10,200 full palmprints to test the proposed system. Despite the inherent difficulty of latent-to-full palmprint matching, rank-1 recognition rates of 78.7 and 69 percent, respectively, were achieved in searching live-scan partial palmprints and latent palmprints against the background database.

  20. A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children

    Science.gov (United States)

    Persaud, Deborah; Pierson, Theodore; Ruff, Christian; Finzi, Diana; Chadwick, Karen R.; Margolick, Joseph B.; Ruff, Andrea; Hutton, Nancy; Ray, Stuart; Siliciano, Robert F.

    2000-01-01

    HIV-1 persists in a latent state in resting CD4+ T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4+ T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4+ T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1–3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4+ T cells will be a major obstacle to HIV-1 eradication in children. PMID:10749578

  1. Detección del virus del enanismo amarillo de la cebolla (OYDV y el virus latente común del ajo (GCLV en ajo (Allium sativum L costarricense

    Directory of Open Access Journals (Sweden)

    Anny Vannesa Guillén Watson

    2011-05-01

    Full Text Available Las enfermedades virales son responsables de pérdidas importantes en el rendimiento del cultivo de ajo alrededor del mundo, ya que limitan su producción. En esta investigación se analizó material de ajo costarricense para determinar la incidencia de los virus: Garlic Common Latent Virus (GCLV y Onion Yellow Dwarf Virus (OYDV, mediante la técnica DAS-ELISA, con el fin de conocer el estado fitosanitario del material criollo. Se utilizaron bulbos de campo de apariencia normal (N, normales con túnica amarilla (TA y con deformaciones (D; y hojas de campo normales (N, sintomáticas (S y con presencia de posibles vectores  virales (VT. Se analizaron vitroplantas producto de la introducción de ápices de 1,0 y 0,5cm de longitud procedentes de dientes normales (N y con túnica amarilla (TA; así como dos lotes de bulbillos obtenidos in vitro de introducciones de ápices de 1,0cm de largo a partir de bulbos de apariencia normal. Se encontró que el 33% de los bulbos de campo analizados para GCLV fueron positivos (TA, mientras que OYDV se detectó en el 100%, sin importar la apariencia. El 100% de las hojas fue positivo para GCLV, y para OYDV soloaquellas de apariencia normal (33%. El 100% de las vitroplantas no presentaron infección de GCLV, mientras que para OYDV solo las introducidas de ápices de 1,0cm provenientes de bulbos con túnica amarillenta no mostraron incidencia. Se determinó GCLV en el 100% de lasmuestras para ambos lotes de bulbificación in Vitro, y OYDV solo en el 50%. Se concluye que los virus OYDV y GCLV están presentes en el ajo costarricense y se detectaron mediante la técnica DASELISA, con una alta incidencia en el material local y con infección diferencial según el órgano analizado. Se recomienda combinar diversas metodologías junto con el cultivo de ápices in vitro, para obtener mayor eficacia en la limpieza viral, lo que contribuiría a incrementar el valor y potenciar el cultivo de la semilla local.

  2. 3-Econsystems: MicroRNAs, Receptors, and Latent Viruses; Some Insights Biology Can Gain from Economic Theory.

    Science.gov (United States)

    Polansky, Hanan; Javaherian, Adrian

    2016-01-01

    This mini-review describes three biological systems. All three include competing molecules and a limiting molecule that binds the competing molecules. Such systems are extensively researched by economists. In fact, the issue of limited resources is the defining feature of economic systems. Therefore, we call these systems "econsystems." In an econsystem, the allocation of the limiting molecule between the competing molecules determines the behavior of the system. A cell is an example of an econsystem. Therefore, a change in the allocation of a limiting molecule as a result of, for instance, an abnormal change in the concentration of one of the competing molecules, may result in abnormal cellular behavior, and disease. The first econsystem described in this mini-review includes a long non-coding RNA and a messenger RNA (lncRNA and mRNA). The limiting molecule is a microRNA (miRNA). The lncRNA and mRNA are known as competing endogenous RNAs (ceRNAs). The second econsystem includes two receptors, and the limiting molecule is a ligand. The third econsystem includes a cis-regulatory element of a latent virus and that of a human gene. The limiting molecule is a transcription complex that binds both cis-elements.

  3. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  4. Detection of viruses in olive trees in Croatian Istria

    Directory of Open Access Journals (Sweden)

    Marta LUIGI

    2011-05-01

    Full Text Available Normal 0 14 false false false IT ZH-TW X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabella normale"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Following identification of four viruses in a general survey of olive trees throughout Croatia, a detailed survey was conducted in 2009 in the field collection of the Institute of Agriculture and Tourism in Poreč (an important reservoir of Istrian native olive germplasm in order to evaluate the sanitary status of the most important Croatian Istria olive cultivars. Twenty five samples from symptomatic or symptomless trees were collected from five autochthonous and four exotic cultivars. All the samples were tested by RT-PCR for the presence of: Olive leaf yellowing associated virus (OLYaV, Cherry leaf roll virus (CLRV, Strawberry latent ring spot virus (SLRSV, Arabis mosaic virus (ArMV, Olive latent virus-1 (OLV-1, Cucumber mosaic virus (CMV, Olive latent virus-2 (OLV-2 and Tobacco necrosis virus D (TNV-D. Six of the 25 plants were found positive to CLRV; all infected plants showed leaf and fruit deformation and leaf yellowing. Four positive samples were from the native cv. Buža whereas the other two were from two exotic cultivars: Ascolana tenera and Frantoio. The presence of CLRV,  either in native or imported plants, highlights the importance of strict phytosanitary regulations to prevent incursion of key

  5. The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

    Science.gov (United States)

    Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.; Siliciano, Robert F.

    2016-01-01

    Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID:27382129

  6. General properties of grapevine viruses occurring in Hungary

    Directory of Open Access Journals (Sweden)

    Eszter Cseh

    2012-03-01

    Full Text Available The past fifty years important advances have been made in the field of grapevine virus research, including characterization of pathogens and control measurements. Still the occurrence of Grapevine fanleaf virus (GFLV, Arabis mosaic virus (ArMV, Tomato black ring virus (TBRV, Grapevine chrome mosaic virus (GCMV, Alfalfa mosaic virus (AMV, Grapevine Bulgarian latent virus (GBLV, Grapevine fleck virus (GFkV, Grapevine leafroll- associated viruses (GLRaV1-4, Grapevine virus A (GVA, Grapevine virus B (GVB and Grapevine rupestris stem pitting- associated virus (GRSPaV have been reported in Hungary and characterized by conventional methods as woody indexing, herbaceous indexing and serological methods. Among grapevine viruses the Grapevine line pattern virus (GLPV seems to be uncial; because it was reported only in Hungary. Causal agents of several grapevine diseases, like enation, vein necrosis and vein mosaic remained undiscovered. These virus-like diseases occurred only sporadically, without economic importance.

  7. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  8. Atypical manifestations of Epstein–Barr virus in children: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Vasileios Bolis

    2016-03-01

    Full Text Available Objective: Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein–Barr virus infection. Sources: Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus. Computer searches used combinations of key words relating to “EBV infections” and “atypical manifestation.” Summary of the findings: Epstein–Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein–Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein–Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Conclusions: Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. Resumo: Objetivo: Esclarecimento da frequência e dos mecanismos patofisiológicos das manifestações raras da infecção por vírus de Epstein–Barr. Fontes: Estudos de pesquisas originais publicados em inglês entre 1985 e 2015 foram selecionados por meio de uma busca na literatura assistida por computador (Pubmed e Scopus. As buscas no computador utilizaram combinações de palavras-chave relacionadas a “infecções por VEB” e “manifestação at

  9. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate.

    OpenAIRE

    Coen, D M; Kosz-Vnenchak, M; Jacobson, J G; Leib, D A; Bogard, C L; Schaffer, P A; Tyler, K L; Knipe, D M

    1989-01-01

    Herpes simplex virus infection of mammalian hosts involves lytic replication at a primary site, such as the cornea, translocation by axonal transport to sensory ganglia and replication, and latent infection at a secondary site, ganglionic neurons. The virus-encoded thymidine kinase, which is a target for antiviral drugs such as acyclovir, is not essential for lytic replication yet evidently is required at the secondary site for replication and some phase of latent infection. To determine the ...

  10. No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

    Science.gov (United States)

    Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

    2010-01-01

    Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

  11. Viruses of foodborne origin: a review

    Directory of Open Access Journals (Sweden)

    Todd EC

    2015-04-01

    Full Text Available Ewen CD Todd,1,2 Judy D Greig3 1Ewen Todd Consulting LLC, Okemos, MI, USA; 2Department of Nutrition and Food Science, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut, Lebanon; 3Division of Public Health Risk Sciences, Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, ON, Canada Abstract: Enteric viruses are major contributors to foodborne disease, and include adenovirus, astrovirus, rotavirus, sapovirus, hepatitis A and E viruses, and norovirus. From a foodborne transmission perspective, norovirus is the most important; however, hepatitis A is associated with more serious illness. Foodborne viruses are transmitted through contaminated food, but also in combination with person-to-person contact or through environmental contamination. These viruses survive well in the environment, are excreted in abundance in feces, and have a low infectious dose, all of which facilitate spread within a community. Many colonized individuals experience mild gastroenteritis lasting a few days or are asymptomatic, although viral excretion may continue over days or weeks. Severe illness tends to be restricted to the very young and elderly, especially in closed communities such as schools and homes for the aged. In the USA, norovirus is considered to be responsible for two thirds of all foodborne illnesses occurring in a wide range of institutional settings, including schools, colleges, child care centers, cruise ships, prisons, and soldiers on campaign. Norovirus outbreaks also occur at one-time events, such as banquets, wedding receptions, birthday parties, and potluck meals, and are most often introduced by infected food workers producing, preparing, or serving food, or through self-service buffets. Often the infections are introduced from the community into institutions where they can infect the majority of residents unless quickly controlled. In countries where economic assessments have been completed

  12. Role of latent membrane protein 1 in chronic active Epstein–Barr virus infection-derived T/NK-cell proliferation

    International Nuclear Information System (INIS)

    Ito, Takuto; Kawazu, Hidetaka; Murata, Takayuki; Iwata, Seiko; Arakawa, Saki; Sato, Yoshitaka; Kuzushima, Kiyotaka; Goshima, Fumi; Kimura, Hiroshi

    2014-01-01

    Epstein–Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line

  13. From where did the 2009 'swine-origin' influenza A virus (H1N1 emerge?

    Directory of Open Access Journals (Sweden)

    Armstrong John S

    2009-11-01

    Full Text Available Abstract The swine-origin influenza A (H1N1 virus that appeared in 2009 and was first found in human beings in Mexico, is a reassortant with at least three parents. Six of the genes are closest in sequence to those of H1N2 'triple-reassortant' influenza viruses isolated from pigs in North America around 1999-2000. Its other two genes are from different Eurasian 'avian-like' viruses of pigs; the NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993, and the MP gene is closest to H3N2 viruses isolated in Asia in 1999-2000. The sequences of these genes do not directly reveal the immediate source of the virus as the closest were from isolates collected more than a decade before the human pandemic started. The three parents of the virus may have been assembled in one place by natural means, such as by migrating birds, however the consistent link with pig viruses suggests that human activity was involved. We discuss a published suggestion that unsampled pig herds, the intercontinental live pig trade, together with porous quarantine barriers, generated the reassortant. We contrast that suggestion with the possibility that laboratory errors involving the sharing of virus isolates and cultured cells, or perhaps vaccine production, may have been involved. Gene sequences from isolates that bridge the time and phylogenetic gap between the new virus and its parents will distinguish between these possibilities, and we suggest where they should be sought. It is important that the source of the new virus be found if we wish to avoid future pandemics rather than just trying to minimize the consequences after they have emerged. Influenza virus is a very significant zoonotic pathogen. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events involving the virus. Measures that might restore confidence include establishing a unified international administrative

  14. Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

    Science.gov (United States)

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

    2014-05-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

  15. Evidence for a Euro-American origin of human immunodeficiency virus (HIV).

    Science.gov (United States)

    Katner, H P; Pankey, G A

    1987-10-01

    Recent reports of the nonspecificity of the enzyme-linked immunosorbent assay (ELISA) test in African populations, significant genomic differences between simian T-cell lymphotropic virus and human immunodeficiency virus (HIV), and the early appearance of clinical acquired immunodeficiency syndroME (AIDS) in the US and Europe are powerful arguments against the assumption that AIDS originated in Africa. The authors postulate that HIV infection has been endemic in the Euro-American population at least since the beginning of the 20th century and that sociocultural changes led to the introduction of the virus into Africa. A search of the literature reveals 28 cases of disseminated Kaposi's sarcoma in the pre-epidemic 1902-66 period. In none of these cases are notations made on intravenous drug abuse, homosexuality, or other risk factors for AIDS. The majority of cases involved men, however. It is pointed out that, in a population where the incidence of a virus such as HIV is low, the number of sexual partners is limited, and intravenous drug abuse is nonexistent, an infection with as long a latency period as HIV may not only be expressed sporadically, but would probably not be recognized as a transmissible infection. On the other hand, the significant changes in these social factors that occurred as a result of the sexual revolution of the late 1960s and early 1970s would be expected to increase the spread of infection and clinical disease so that recognition would be achieved. During the past decade, there have been marked increases in the number of sexually transmitted infections in the homosexual male population. The efficiency of anal intercourse as a mode of transmission probably accounts for the fact that HIV infection first expressed itself in this population.

  16. Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection

    Directory of Open Access Journals (Sweden)

    Benjamin A. Krishna

    2017-12-01

    Full Text Available Reactivation of human cytomegalovirus (HCMV latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR, which, during lytic infection, is a constitutive cell-signaling activator. Here we now show that in monocytes, which are recognized sites of HCMV latency in vivo, US28 attenuates multiple cell signaling pathways, including mitogen-activated protein (MAP kinase and NF-κB, and that this is required to establish a latent infection; viruses deleted for US28 initiate a lytic infection in infected monocytes. We also show that these monocytes then become potent targets for the HCMV-specific host immune response and that latently infected cells treated with an inverse agonist of US28 also reactivate lytic infection and similarly become immune targets. Consequently, we suggest that the use of inhibitors of US28 could be a novel immunotherapeutic strategy to reactivate the latent viral reservoir, allowing it to be targeted by preexisting HCMV-specific T cells.

  17. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Klein, George, E-mail: Georg.Klein@ki.se [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden); Klein, Eva; Kashuba, Elena [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden)

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  18. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    International Nuclear Information System (INIS)

    Klein, George; Klein, Eva; Kashuba, Elena

    2010-01-01

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  19. Short communication: isolation and phylogenetic analysis of an avian-origin H3N2 canine influenza virus in dog shelter, China.

    Science.gov (United States)

    Su, Shuo; Yuan, Ziguo; Chen, Jidang; Xie, Jiexiong; Li, Huatao; Huang, Zhen; Zhang, Minze; Du, Guohao; Chen, Zhongming; Tu, Liqing; Zou, Yufei; Miao, Junhao; Wang, Hui; Jia, Kun; Li, Shoujun

    2013-06-01

    A H3N2 canine influenza virus, A/canine/Guangdong/3/2011 (H3N2), was isolated from roaming dogs in rural China. Sequence and phylogenetic analysis of eight gene segments revealed that the A/canine/Guangdong/3/2011 (H3N2) was most similar to a recent H3N2 canine influenza virus isolated in cats from South Korea, which originated from an avian strain. To our knowledge, this is the first report of an avian-origin H3N2 CIV which was isolated from roaming dogs in China. The epidemiologic information provided herein suggests that continued study is required to determine if this virus could be established in the roaming dog population in rural China and pose potential threats to public health.

  20. Viruses and kidney disease: beyond HIV.

    Science.gov (United States)

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B

    2008-11-01

    Human immunodeficiency virus (HIV)-infected patients may acquire new viral co-infections; they also may experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections owing to immunodeficiency or risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.

  1. Multiplex real-time PCR for the detection and quantification of latent and persistent viral genomes in cellular or plasma blood fractions.

    Science.gov (United States)

    Compston, Lara Isobel; Sarkobie, Francis; Li, Chengyao; Candotti, Daniel; Opare-Sem, Ohene; Allain, Jean-Pierre

    2008-07-01

    In common with latent viruses such as herpesviruses, parvovirus B19, HBV and GBV-C are contained successfully by the immune response and persist in the host. When immune control breaks down, reactivation of both latent and persistent viruses occurs. Two multiplex assays were developed (B19, HBV, HHV-8), (EBV, CMV, VZV) for blood screening, and tested on blood donor samples from Ghana to determine baseline prevalence of viraemia in immunocompetent persons. Single-virus real-time quantitative PCR (qPCR) assays were optimised for viral load determination of positive initial screening. The qPCR method utilised was absolute quantification with external standards. Multiplex and single-virus qPCR assays had similar sensitivity, except for the B19 assay in which sensitivity was 100-fold lower. Assays were optimised for reproducibility and repeatability, with R(2) of 0.9 being obtained for most assays. With the exception of B19 and CMV, assays had 100% detection limit ranging between 10(1) and 10(2) copies, IU or arbitrary units under single-virus and multiplex assay conditions. The prevalence of viraemia was 1.6% HBV (0.8% DNA+/HBsAg-, 0.8% DNA+/HBsAg+), 0.8% parvovirus B19, and 3.3% GBV-C viraemia in the plasma fraction. The prevalence of four herpesviruses was 1.0% HHV-8, 0.85% CMV, and 8.3% EBV, and no detectable VZV viraemia.

  2. Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing.

    Science.gov (United States)

    Senkevich, Tatiana G; Bruno, Daniel; Martens, Craig; Porcella, Stephen F; Wolf, Yuri I; Moss, Bernard

    2015-09-01

    Poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded DNA genomes. Nevertheless, the mode of poxvirus DNA replication and the nature and location of the replication origins remain unknown. A current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subsequently resolved into unit genomes. The existence of specific origins has been questioned because any plasmid can replicate in cells infected by vaccinia virus (VACV), the prototype poxvirus. We applied directional deep sequencing of short single-stranded DNA fragments enriched for RNA-primed nascent strands isolated from the cytoplasm of VACV-infected cells to pinpoint replication origins. The origins were identified as the switching points of the fragment directions, which correspond to the transition from continuous to discontinuous DNA synthesis. Origins containing a prominent initiation point mapped to a sequence within the hairpin loop at one end of the VACV genome and to the same sequence within the concatemeric junction of replication intermediates. These findings support a model for poxvirus genome replication that involves leading and lagging strand synthesis and is consistent with the requirements for primase and ligase activities as well as earlier electron microscopic and biochemical studies implicating a replication origin at the end of the VACV genome.

  3. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico.

    Science.gov (United States)

    Meacham, Meredith C; Roesch, Scott C; Strathdee, Steffanie A; Lindsay, Suzanne; Gonzalez-Zuniga, Patricia; Gaines, Tommi L

    2018-01-01

    Patterns of polydrug use among people who inject drugs (PWID) may be differentially associated with overdose and unique human immunodeficiency virus (HIV) risk factors. Subgroups of PWID in Tijuana, Mexico, were identified based on substances used, route of administration, frequency of use and co-injection indicators. Participants were PWID residing in Tijuana age ≥18 years sampled from 2011 to 2012 who reported injecting an illicit substance in the past month (n = 735). Latent class analysis identified discrete classes of polydrug use characterised by 11 indicators of past 6 months substance use. Multinomial logistic regression examined class membership association with HIV risk behaviours, overdose and other covariates using an automated three-step procedure in mplus to account for classification error. Participants were classified into five subgroups. Two polydrug and polyroute classes were defined by use of multiple substances through several routes of administration and were primarily distinguished from each other by cocaine use (class 1: 5%) or no cocaine use (class 2: 29%). The other classes consisted primarily of injectors: cocaine, methamphetamine and heroin injection (class 3: 4%); methamphetamine and heroin injection (class 4: 10%); and heroin injection (class 5: 52%). Compared with the heroin-only injection class, memberships in the two polydrug and polyroute use classes were independently associated with both HIV injection and sexual risk behaviours. Substance use patterns among PWID in Tijuana are highly heterogeneous, and polydrug and polyroute users are a high-risk subgroup who may require more tailored prevention and treatment interventions. [Meacham MC, Roesch SC, Strathdee SA, Lindsay S, Gonzalez-Zuniga P, Gaines TL. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico. Drug Alcohol Rev 2018;37:128-136].

  4. Evolutionary patterns in the sequence and structure of transfer RNA: early origins of archaea and viruses.

    Directory of Open Access Journals (Sweden)

    Feng-Jie Sun

    2008-03-01

    Full Text Available Transfer RNAs (tRNAs are ancient molecules that are central to translation. Since they probably carry evolutionary signatures that were left behind when the living world diversified, we reconstructed phylogenies directly from the sequence and structure of tRNA using well-established phylogenetic methods. The trees placed tRNAs with long variable arms charging Sec, Tyr, Ser, and Leu consistently at the base of the rooted phylogenies, but failed to reveal groupings that would indicate clear evolutionary links to organismal origin or molecular functions. In order to uncover evolutionary patterns in the trees, we forced tRNAs into monophyletic groups using constraint analyses to generate timelines of organismal diversification and test competing evolutionary hypotheses. Remarkably, organismal timelines showed Archaea was the most ancestral superkingdom, followed by viruses, then superkingdoms Eukarya and Bacteria, in that order, supporting conclusions from recent phylogenomic studies of protein architecture. Strikingly, constraint analyses showed that the origin of viruses was not only ancient, but was linked to Archaea. Our findings have important implications. They support the notion that the archaeal lineage was very ancient, resulted in the first organismal divide, and predated diversification of tRNA function and specificity. Results are also consistent with the concept that viruses contributed to the development of the DNA replication machinery during the early diversification of the living world.

  5. Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus

    Directory of Open Access Journals (Sweden)

    Wen Su

    2015-09-01

    Full Text Available Since 2013, avian influenza A(H7N9 viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially H9N2, in Chinese poultry. Despite concerns about the pandemic threat posed by H7N9 viruses, little is known about the biological properties of H7N9 viruses that may recruit internal genes from genetically distinct H9N2 viruses circulating among wild birds. Here, we generated 63 H7N9 reassortants derived from an avian H7N9 and a wild-bird-origin H9N2 virus. Compared with the wild-type parent, 25/63 reassortants had increased pathogenicity in mice. A reassortant containing PB1 of the H9N2 virus was highly lethal to mice and chickens but was not transmissible to guinea pigs by airborne routes; however, three substitutions associated with adaptation to mammals conferred airborne transmission to the virus. The emergence of the H7N9-pandemic reassortant virus highlights that continuous monitoring of H7N9 viruses is needed, especially at the domestic poultry/wild bird interface.

  6. Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

    2015-10-29

    Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

  7. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.

    2011-01-01

    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...... in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods: This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I...... and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig...

  8. Viruses & kidney disease: beyond HIV

    Science.gov (United States)

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B.

    2008-01-01

    HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA. PMID:19013331

  9. Latent-trait latent-class analysis of selfdisclosure in the work environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2006-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  10. Latent-trait latent-class analysis of selfdisclosure in the work environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  11. The effects of Epstein-Barr virus-encoded latent membrane protein-1 in the irradiated nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Hsu, H.-Y.; Hsu, W.-L.

    2003-01-01

    Full text: Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan. NPC is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 (LMP-1)is commonly found in the tumor cells. Radiotherapy is the effective choice for most of the NPC patients with different classification and stages. The previous studies showed that EBV-associated NPC tend to be more sensitive to radiotherapy and have been shown the better prognosis than that of EBV-negative NPC. It suggests that LMP-1 may be able to modulate the cellular sensitivity of apoptosis induced by radiation in some kinds of NPC cells. In our study, LMP-1-expressing HONE-1 NPC cells were taken to treat with radiation to investigate whether the LMP-1 can prevent the cells from apoptosis induced by irradiation. The growth of LMP-1-expressing HONE-1 NPC cells were not significantly different from that without expressing LMP-1 at a giving dose of 2, 4 or 6Gy. However, the arrested cellular growth was found in LMP-1-expressing cells irradiated with a dose higher than 8Gy. In addition to the DNA fragmentation, the different levels of several related proteins of the apoptotic pathway and the mRNA of cell cycle arrest in these transfected cells were also investigated after various treatments

  12. Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010.

    Science.gov (United States)

    Shu, Bo; Garten, Rebecca; Emery, Shannon; Balish, Amanda; Cooper, Lynn; Sessions, Wendy; Deyde, Varough; Smith, Catherine; Berman, LaShondra; Klimov, Alexander; Lindstrom, Stephen; Xu, Xiyan

    2012-01-05

    Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between 1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from 1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inheriting genes from classical swine, avian and human influenza viruses. Of those twenty-one tr_SOIV, thirteen were of A(H1N1), one of A(H1N2), and seven of A(H3N2) subtype. SOIV characterized were antigenically and genetically closely related to the subtypes of influenza viruses circulating in pigs but distinct from contemporary influenza viruses circulating in humans. The diversity of subtypes and genetic lineages in SOIV cases highlights the importance of continued surveillance at the animal-human interface. Copyright © 2011. Published by Elsevier Inc.

  13. Complete nucleotide sequence and genome structure of a Japanese isolate of hibiscus latent Fort Pierce virus, a unique tobamovirus that contains an internal poly(A) region in its 3' end.

    Science.gov (United States)

    Yoshida, Tetsuya; Kitazawa, Yugo; Komatsu, Ken; Neriya, Yutaro; Ishikawa, Kazuya; Fujita, Naoko; Hashimoto, Masayoshi; Maejima, Kensaku; Yamaji, Yasuyuki; Namba, Shigetou

    2014-11-01

    In this study, we detected a Japanese isolate of hibiscus latent Fort Pierce virus (HLFPV-J), a member of the genus Tobamovirus, in a hibiscus plant in Japan and determined the complete sequence and organization of its genome. HLFPV-J has four open reading frames (ORFs), each of which shares more than 98 % nucleotide sequence identity with those of other HLFPV isolates. Moreover, HLFPV-J contains a unique internal poly(A) region of variable length, ranging from 44 to 78 nucleotides, in its 3'-untranslated region (UTR), as is the case with hibiscus latent Singapore virus (HLSV), another hibiscus-infecting tobamovirus. The length of the HLFPV-J genome was 6431 nucleotides, including the shortest internal poly(A) region. The sequence identities of ORFs 1, 2, 3 and 4 of HLFPV-J to other tobamoviruses were 46.6-68.7, 49.9-70.8, 31.0-70.8 and 39.4-70.1 %, respectively, at the nucleotide level and 39.8-75.0, 43.6-77.8, 19.2-70.4 and 31.2-74.2 %, respectively, at the amino acid level. The 5'- and 3'-UTRs of HLFPV-J showed 24.3-58.6 and 13.0-79.8 % identity, respectively, to other tobamoviruses. In particular, when compared to other tobamoviruses, each ORF and UTR of HLFPV-J showed the highest sequence identity to those of HLSV. Phylogenetic analysis showed that HLFPV-J, other HLFPV isolates and HLSV constitute a malvaceous-plant-infecting tobamovirus cluster. These results indicate that the genomic structure of HLFPV-J has unique features similar to those of HLSV. To our knowledge, this is the first report of the complete genome sequence of HLFPV.

  14. National policies on the management of latent tuberculosis infection: review of 98 countries

    Science.gov (United States)

    Jagger, Ann; Reiter-karam, Silke; Getahun, Haileyesus

    2018-01-01

    Abstract Objective To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. Methods We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. Findings We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries’ policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. Conclusion Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies. PMID:29531416

  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. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells.

    Science.gov (United States)

    Huang, Szu-Han; Ren, Yanqin; Thomas, Allison S; Chan, Dora; Mueller, Stefanie; Ward, Adam R; Patel, Shabnum; Bollard, Catherine M; Cruz, Conrad Russell; Karandish, Sara; Truong, Ronald; Macedo, Amanda B; Bosque, Alberto; Kovacs, Colin; Benko, Erika; Piechocka-Trocha, Alicja; Wong, Hing; Jeng, Emily; Nixon, Douglas F; Ho, Ya-Chi; Siliciano, Robert F; Walker, Bruce D; Jones, R Brad

    2018-02-01

    The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells. Here, we have shown that treating CD4+ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8+ T cells recognized and potently eliminated CD4+ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8+ T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to CD8+ T cells that may need to be addressed to cure infection.

  17. Radioimmunoassay of Herpes simplex virus antibody: correlation with ganglionic infection

    International Nuclear Information System (INIS)

    Forghani, B.; Klassen, T.; Baringer, J.R.

    1977-01-01

    Results of herpes simplex virus (HSV) isolation from a series of human post-mortem trigeminal thoracic and sacral ganglia were correlated with HSV antibody type(s) detected in the sera by radioimmunoassay (RIA). HSV type I was isolated from trigeminal ganglia of 44 out of 90 individuals, from thoracic ganglia of 1 out of 25, and from sacral ganglia of 1 out of 68 cases. HSV type was recovered from sacral ganglia of 8 out of 68 individuals. In all cases in which an HSV was isolated from ganglia and was available for testing, homologous, type-specific antibody was demonstrable, and in a few instances antibody to the heterologous HSV was also detected. In those individuals in which HSV type I was isolated from trigeminal ganglia and HSV type 2 from sacral ganglia, antibody to both virus types was present in the sera, indicating that simultaneous latent infections with each of the two viruses can occur, and that antibody is produced to each virus independently. Antibody to HSV type 1, 2 or both types was demonstrated in 8 out of 10 cases in which virus isolation attempts were negative, suggesting either a higher sensitivity of RIA for detecting HSV infection, or the presence of latent HSV at some other site in the body which was not sampled. (author)

  18. Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.

    Science.gov (United States)

    Sun, Hailiang; Blackmon, Sherry; Yang, Guohua; Waters, Kaitlyn; Li, Tao; Tangwangvivat, Ratanaporn; Xu, Yifei; Shyu, Daniel; Wen, Feng; Cooley, Jim; Senter, Lucy; Lin, Xiaoxu; Jarman, Richard; Hanson, Larry; Webby, Richard; Wan, Xiu-Feng

    2017-11-01

    Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus (CIV) H3N2 (CIV-H3N2) and equine-origin CIV H3N8 (CIV-H3N8), are enzootic in the canine population. Dogs have been demonstrated to seroconvert in response to diverse IAVs, and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antiserum, we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting that there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2 × pandemic H1N1 (pdmH1N1) reassortants by characterizing their in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1, identifying some combinations that were more active than either parental virus complex. Using reverse genetics and fixing the CIV-H3N2 hemagglutinin (HA), we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high-growth phenotypes in vitro , and 13 of these replicated in mouse lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant was efficiently transmitted by contact but not by the airborne route and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs. IMPORTANCE IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained transmission into a human population with limited herd immunity. Dogs are a a potential mixing vessel for avian

  19. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    Science.gov (United States)

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2015-03-02

    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

    Science.gov (United States)

    Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2015-04-01

    The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2

  1. Bovine herpes virus infections in cattle.

    Science.gov (United States)

    Nandi, S; Kumar, Manoj; Manohar, M; Chauhan, R S

    2009-06-01

    Bovine herpes virus 1 (BHV-1) is primarily associated with clinical syndromes such as rhinotracheitis, pustular vulvovaginitis and balanoposthitis, abortion, infertility, conjunctivitis and encephalitis in bovine species. The main sources of infection are the nasal exudates and the respiratory droplets, genital secretions, semen, fetal fluids and tissues. The BHV-1 virus can become latent following a primary infection with a field isolate or vaccination with an attenuated strain. The viral genomic DNA has been demonstrated in the sensory ganglia of the trigeminal nerve in infectious bovine rhinotracheitis (IBR) and in sacral spinal ganglia in pustular vulvovaginitis and balanoposthitis cases. BHV-1 infections can be diagnosed by detection of virus or virus components and antibody by serological tests or by detection of genomic DNA by polymerase chain reaction (PCR), nucleic acid hybridization and sequencing. Inactivated vaccines and modified live virus vaccines are used for prevention of BHV-1 infections in cattle; subunit vaccines and marker vaccines are under investigation.

  2. Latent-Trait Latent-Class Analysis of Self-disclosure in the Work Environment

    NARCIS (Netherlands)

    Maij - de Meij, A.M.; Kelderman, H.; van der Flier, H.

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of

  3. 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,

  4. Latent classification models

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre

    2005-01-01

    parametric family ofdistributions.  In this paper we propose a new set of models forclassification in continuous domains, termed latent classificationmodels. The latent classification model can roughly be seen ascombining the \\NB model with a mixture of factor analyzers,thereby relaxing the assumptions...... classification model, and wedemonstrate empirically that the accuracy of the proposed model issignificantly higher than the accuracy of other probabilisticclassifiers....

  5. Nicotiana small RNA sequences support a host genome origin of cucumber mosaic virus satellite RNA.

    Directory of Open Access Journals (Sweden)

    Kiran Zahid

    2015-01-01

    Full Text Available Satellite RNAs (satRNAs are small noncoding subviral RNA pathogens in plants that depend on helper viruses for replication and spread. Despite many decades of research, the origin of satRNAs remains unknown. In this study we show that a β-glucuronidase (GUS transgene fused with a Cucumber mosaic virus (CMV Y satellite RNA (Y-Sat sequence (35S-GUS:Sat was transcriptionally repressed in N. tabacum in comparison to a 35S-GUS transgene that did not contain the Y-Sat sequence. This repression was not due to DNA methylation at the 35S promoter, but was associated with specific DNA methylation at the Y-Sat sequence. Both northern blot hybridization and small RNA deep sequencing detected 24-nt siRNAs in wild-type Nicotiana plants with sequence homology to Y-Sat, suggesting that the N. tabacum genome contains Y-Sat-like sequences that give rise to 24-nt sRNAs capable of guiding RNA-directed DNA methylation (RdDM to the Y-Sat sequence in the 35S-GUS:Sat transgene. Consistent with this, Southern blot hybridization detected multiple DNA bands in Nicotiana plants that had sequence homology to Y-Sat, suggesting that Y-Sat-like sequences exist in the Nicotiana genome as repetitive DNA, a DNA feature associated with 24-nt sRNAs. Our results point to a host genome origin for CMV satRNAs, and suggest novel approach of using small RNA sequences for finding the origin of other satRNAs.

  6. Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function.

    Science.gov (United States)

    Wong, S W; Schaffer, P A

    1991-05-01

    Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.

  7. Viral meningitis epidemics and a single, recent, recombinant and anthroponotic origin of swine vesicular disease virus

    DEFF Research Database (Denmark)

    Bruhn, Christian Anders Wathne; Nielsen, Sandra Cathrine Abel; Samaniego Castruita, Jose Alfredo

    2015-01-01

    BACKGROUND AND OBJECTIVES: Swine vesicular disease virus (SVDV) is a close relative of the human Enterovirus B serotype, coxsackievirus B5. As the etiological agent of a significant emergent veterinary disease, several studies have attempted to explain its origin. However, several key questions...... and non-coding regions supports that SVDV has a recombinant origin between coxsackievirus B5 and another Enterovirus B serotype, most likely coxsackievirus A9. Extensive Bayesian sequence-based analysis of the time of the most recent common ancestor of all analysed sequences places this within a few years...... around 1961. Epidemiological evidence points to China as an origin, but there are no available samples to test this conclusively. CONCLUSIONS AND IMPLICATIONS: Historical investigation and the clinical aspects of the involved Enterovirus B serotypes, makes the current results consistent with a hypothesis...

  8. The molecular basis of herpes simplex virus latency

    Science.gov (United States)

    Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

    2012-01-01

    Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation. This review considers current knowledge and hypotheses relating to the mechanisms involved in the establishment, maintenance and reactivation herpes simplex virus latency. PMID:22150699

  9. The biology of herpes simplex virus infection in humans.

    Science.gov (United States)

    Baringer, J R

    1976-01-01

    Herpes simplex virus is a frequent cause of recurrent ocular, oral, genital or cutaneous eruptions in man. Lesions are highly localized and tend to recur at the same site. Among the most consistent factors provoking recurrence is root section of the trigeminal nerve. Clinical and experimental data suggest that herpes simplex virus is commonly resident within the trigeminal ganglia of man, where it may be responsible for recurrent oral or lip lesions, and is less frequently a resident of the second or third sacral ganglia where it might be responsible for genital eruptions. Generally, the trigeminal virus is type 1 and the sacral virus is type 2; the virus is only rarely recoverable from other sensory ganglia. Factors provoking the reactivation from the virus' latent site and the mechanism for reactivation remain largely unknown. Further study is needed to understand the behavior of HSV and other viruses in nervous system tissue.

  10. Hibiscus latent Fort Pierce virus in Brazil and synthesis of its biologically active full-length cDNA clone.

    Science.gov (United States)

    Gao, Ruimin; Niu, Shengniao; Dai, Weifang; Kitajima, Elliot; Wong, Sek-Man

    2016-10-01

    A Brazilian isolate of Hibiscus latent Fort Pierce virus (HLFPV-BR) was firstly found in a hibiscus plant in Limeira, SP, Brazil. RACE PCR was carried out to obtain the full-length sequences of HLFPV-BR which is 6453 nucleotides and has more than 99.15 % of complete genomic RNA nucleotide sequence identity with that of HLFPV Japanese isolate. The genomic structure of HLFPV-BR is similar to other tobamoviruses. It includes a 5' untranslated region (UTR), followed by open reading frames encoding for a 128-kDa protein and a 188-kDa readthrough protein, a 38-kDa movement protein, 18-kDa coat protein, and a 3' UTR. Interestingly, the unique feature of poly(A) tract is also found within its 3'-UTR. Furthermore, from the total RNA extracted from the local lesions of HLFPV-BR-infected Chenopodium quinoa leaves, a biologically active, full-length cDNA clone encompassing the genome of HLFPV-BR was amplified and placed adjacent to a T7 RNA polymerase promoter. The capped in vitro transcripts from the cloned cDNA were infectious when mechanically inoculated into C. quinoa and Nicotiana benthamiana plants. This is the first report of the presence of an isolate of HLFPV in Brazil and the successful synthesis of a biologically active HLFPV-BR full-length cDNA clone.

  11. Hepatitis E Virus and Related Viruses in Animals.

    Science.gov (United States)

    Thiry, D; Mauroy, A; Pavio, N; Purdy, M A; Rose, N; Thiry, E; de Oliveira-Filho, E F

    2017-02-01

    Hepatitis E is an acute human liver disease in healthy individuals which may eventually become chronic. It is caused by the hepatitis E virus (HEV) and can have a zoonotic origin. Nearly 57,000 people die yearly from hepatitis E-related conditions. The disease is endemic in both developing and developed countries with distinct epidemiologic profiles. In developing countries, the disease is associated with inadequate water treatment, while in developed countries, transmission is associated with animal contact and the ingestion of raw or uncooked meat, especially liver. All human HEV are grouped into at least four genotypes, while HEV or HEV-related viruses have been identified in an increasing number of domestic and wild animal species. Despite a high genetic diversity, only one single HEV serotype has been described to date for HEV genotypes 1-4. The discovery of new HEV or HEV-related viruses leads to a continuing increase in the number of genotypes. In addition, the genome organization of all these viruses is variable with overlapping open reading frames (ORF) and differences in the location of ORF3. In spite of the role of some domestic and wild animals as reservoir, the origin of HEV and HEV-related viruses in humans and animals is still unclear. This review discusses aspects of the detection, molecular virology, zoonotic transmission and origin of HEV and HEV-related viruses in the context of 'One Health' and establishes a link between the previous and the new taxonomy of this growing virus family. © 2015 Blackwell Verlag GmbH.

  12. The Latent Structure of Autistic Traits: A Taxometric, Latent Class and Latent Profile Analysis of the Adult Autism Spectrum Quotient

    Science.gov (United States)

    James, Richard J.; Dubey, Indu; Smith, Danielle; Ropar, Danielle; Tunney, Richard J.

    2016-01-01

    Autistic traits are widely thought to operate along a continuum. A taxometric analysis of Adult Autism Spectrum Quotient data was conducted to test this assumption, finding little support but identifying a high severity taxon. To understand this further, latent class and latent profile models were estimated that indicated the presence of six…

  13. Serology indicates cytomegalovirus infection is associated with varicella-zoster virus reactivation

    OpenAIRE

    OGUNJIMI, Benson; Theeten, Heidi; HENS, Niel; Beutels, Philippe

    2014-01-01

    Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations bet...

  14. 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.

  15. "Latent" infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults.

    Science.gov (United States)

    Cook, Thomas B; Brenner, Lisa A; Cloninger, C Robert; Langenberg, Patricia; Igbide, Ajirioghene; Giegling, Ina; Hartmann, Annette M; Konte, Bettina; Friedl, Marion; Brundin, Lena; Groer, Maureen W; Can, Adem; Rujescu, Dan; Postolache, Teodor T

    2015-01-01

    Latent chronic infection with Toxoplasma gondii (T. gondii), a common neurotropic pathogen, has been previously linked with suicidal self-directed violence (SSDV). We sought to determine if latent infection with T. gondii is associated with trait aggression and impulsivity, intermediate phenotypes for suicidal behavior, in psychiatrically healthy adults. Traits of aggression and impulsivity were analyzed in relationship to IgG antibody seropositivity for T. gondii and two other latent neurotropic infections, herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV). One thousand community-residing adults residing in the Munich metropolitan area with no Axis I or II conditions by SCID for DSM-IV (510 men, 490 women, mean age 53.6 ± 15.8, range 20-74). Plasma samples were tested for IgG antibodies to T. gondii, HSV-1 and CMV by ELISA. Self-reported ratings of trait aggression scores (Questionnaire for Measuring Factors of Aggression [FAF]) and trait impulsivity (Sensation-Seeking Scale-V [SSS-V]) were analyzed using linear multivariate methods. T. gondii IgG seropositivity was significantly associated with higher trait reactive aggression scores among women (p impulsive sensation-seeking (SSS-V Disinhibition) among younger men (p impulsivity, personality traits considered as endophenotypes for SSDV, are associated with latent T. gondii infection in a gender and age-specific manner, and could be further investigated as prognostic and treatment targets in T. gondii-positive individuals at risk for SSDV. Published by Elsevier Ltd.

  16. On the origin and timing of Zika virus introduction in Brazil.

    Science.gov (United States)

    Massad, E; Burattini, M Nascimento; Khan, K; Struchiner, C J; Coutinho, F A B; Wilder-Smith, A

    2017-08-01

    The timing and origin of Zika virus (ZIKV) introduction in Brazil has been the subject of controversy. Initially, it was assumed that the virus was introduced during the FIFA World Cup in June-July 2014. Then, it was speculated that ZIKV may have been introduced by athletes from French Polynesia (FP) who competed in a canoe race in Rio de Janeiro in August 2014. We attempted to apply mathematical models to determine the most likely time window of ZIKV introduction in Brazil. Given that the timing and origin of ZIKV introduction in Brazil may be a politically sensitive issue, its determination (or the provision of a plausible hypothesis) may help to prevent undeserved blame. We used a simple mathematical model to estimate the force of infection and the corresponding individual probability of being infected with ZIKV in FP. Taking into account the air travel volume from FP to Brazil between October 2013 and March 2014, we estimated the expected number of infected travellers arriving at Brazilian airports during that period. During the period between December 2013 and February 2014, 51 individuals travelled from FP airports to 11 Brazilian cities. Basing on the calculated force of ZIKV infection (the per capita rate of new infections per time unit) and risk of infection (probability of at least one new infection), we estimated that 18 (95% CI 12-22) individuals who arrived in seven of the evaluated cities were infected. When basic ZIKV reproduction numbers greater than one were assumed in the seven evaluated cities, ZIKV could have been introduced in any one of the cities. Based on the force of infection in FP, basic reproduction ZIKV number in selected Brazilian cities, and estimated travel volume, we concluded that ZIKV was most likely introduced and established in Brazil by infected travellers arriving from FP in the period between October 2013 and March 2014, which was prior to the two aforementioned sporting events.

  17. Quantification of Human and Animal Viruses to Differentiate the Origin of the Fecal Contamination Present in Environmental Samples

    Directory of Open Access Journals (Sweden)

    Sílvia Bofill-Mas

    2013-01-01

    Full Text Available Many different viruses are excreted by humans and animals and are frequently detected in fecal contaminated waters causing public health concerns. Classical bacterial indicator such as E. coli and enterococci could fail to predict the risk for waterborne pathogens such as viruses. Moreover, the presence and levels of bacterial indicators do not always correlate with the presence and concentration of viruses, especially when these indicators are present in low concentrations. Our research group has proposed new viral indicators and methodologies for determining the presence of fecal pollution in environmental samples as well as for tracing the origin of this fecal contamination (microbial source tracking. In this paper, we examine to what extent have these indicators been applied by the scientific community. Recently, quantitative assays for quantification of poultry and ovine viruses have also been described. Overall, quantification by qPCR of human adenoviruses and human polyomavirus JC, porcine adenoviruses, bovine polyomaviruses, chicken/turkey parvoviruses, and ovine polyomaviruses is suggested as a toolbox for the identification of human, porcine, bovine, poultry, and ovine fecal pollution in environmental samples.

  18. Latent-Trait Latent-Class Analysis of Self-Disclosure in the Work Environment

    Science.gov (United States)

    Maij-de Meij, Annette M.; Kelderman, Henk; van der Flier, Henk

    2005-01-01

    Based on the literature about self-disclosure, it was hypothesized that different groups of subjects differ in their pattern of self-disclosure with respect to different areas of social interaction. An extended latent-trait latent-class model was proposed to describe these general patterns of self-disclosure. The model was used to analyze the data…

  19. New and Emerging Viruses of Blueberry and Cranberry

    Directory of Open Access Journals (Sweden)

    James J. Polashock

    2012-11-01

    Full Text Available Blueberry and cranberry are fruit crops native to North America and they are well known for containing bioactive compounds that can benefit human health. Cultivation is expanding within North America and other parts of the world raising concern regarding distribution of existing viruses as well as the appearance of new viruses. Many of the known viruses of these crops are latent or asymptomatic in at least some cultivars. Diagnosis and detection procedures are often non-existent or unreliable. Whereas new viruses can move into cultivated fields from the wild, there is also the threat that devastating viruses can move into native stands of Vaccinium spp. or other native plants from cultivated fields. The aim of this paper is to highlight the importance of blueberry and cranberry viruses, focusing not only on those that are new but also those that are emerging as serious threats for production in North America and around the world.

  20. New and Emerging Viruses of Blueberry and Cranberry

    Science.gov (United States)

    Martin, Robert R.; Polashock, James J.; Tzanetakis, Ioannis E.

    2012-01-01

    Blueberry and cranberry are fruit crops native to North America and they are well known for containing bioactive compounds that can benefit human health. Cultivation is expanding within North America and other parts of the world raising concern regarding distribution of existing viruses as well as the appearance of new viruses. Many of the known viruses of these crops are latent or asymptomatic in at least some cultivars. Diagnosis and detection procedures are often non-existent or unreliable. Whereas new viruses can move into cultivated fields from the wild, there is also the threat that devastating viruses can move into native stands of Vaccinium spp. or other native plants from cultivated fields. The aim of this paper is to highlight the importance of blueberry and cranberry viruses, focusing not only on those that are new but also those that are emerging as serious threats for production in North America and around the world. PMID:23202507

  1. [Construction and rescue of infectious cDNA clone of pigeon-origin Newcastle disease virus strain JS/07/04/Pi].

    Science.gov (United States)

    Zhu, Yan-Mei; Hu, Zeng-Lei; Song, Qing-Qing; Duan, Zhi-Qiang; Gu, Min; Hu, Shun-Lin; Wang, Xiao-Quan; Liu, Xiu-Fan

    2012-01-01

    Based on the complete genome sequence of pigeon-origin Newcastle disease virus strain JS/07/04/ Pi(genotype VIb), nine overlapped fragments covering its full-length genome were amplified by RT-PCR. The fragments were connected sequentially and then inserted into the transcription vector TVT7/R resulting in the TVT/071204 which contained the full genome of strain JS/07/04/Pi. The TVT/071204 was co-transfected with three helper plasmids pCI-NP, pCI-P and pCI-L into the BSR cells, and the transfected cells and culture supernatant were inoculated into 9-day-old SPF embryonated eggs 60 h post-transfection. The HA and HI tests were conducted following the death of embryonated eggs. The results showed that the allantoic fluids obtained were HA positive and the HA could be inhibited by anti-NDV serum which indicated that the strain JS/07/04/Pi was rescued successfully. The rescued virus rNDV/071204 showed similar growth kinetics to its parental virus in CEF. The successful recovery of this strain would contribute to the understanding of the host-specificity of pigeon-origin NDV and to the development of the novel vaccines against the NDV infection in pigeons.

  2. Identification and characterization of the SSB1 locus involved in symptom development by Spring beauty latent virus infection in Arabidopsis thaliana.

    Science.gov (United States)

    Fujisaki, Koki; Hagihara, Fumi; Azukawa, Yoshihiro; Kaido, Masanori; Okuno, Tetsuro; Mise, Kazuyuki

    2004-09-01

    The natural variation of Arabidopsis thaliana in response to a bromovirus, Spring beauty latent virus (SBLV), was examined. Of 63 Arabidopsis accessions tested, all were susceptible when inoculated with SBLV, although there was a large degree of variation in symptom development. Most accessions, including Columbia (Col-0), were symptomless or developed only mild symptoms, but four accessions, including S96, showed severe symptoms of SBLV infection. Genetic analysis suggested that the difference in the responses of Col-0 and S96 to SBLV was controlled by a single semidominant locus. We have designated this locus SSB1 (symptom development by SBLV infection). By using genetic markers, SSB1 was mapped to chromosome IV. The patterns of distribution and accumulation of SBLV in sensitive accessions were similar to those in the insensitive accessions. In addition, symptom development in S96 by SBLV infection was critically interrupted by the presence of the NahG gene, which encodes salicylic acid (SA) hydroxylase. These data suggest that symptom development in A. thaliana controlled by SSB1 is independent of the efficiency of SBLV multiplication and is dependent on SA signaling.

  3. Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

    Directory of Open Access Journals (Sweden)

    Changyong G

    2010-09-01

    Full Text Available Abstract Dendritic cells (DC are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40 is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4 and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN+ DC were analyzed by flow cytometry (FCM and mixed lymphocyte reaction (MLR. Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

  4. Modeling Nonlinear Change via Latent Change and Latent Acceleration Frameworks: Examining Velocity and Acceleration of Growth Trajectories

    Science.gov (United States)

    Grimm, Kevin; Zhang, Zhiyong; Hamagami, Fumiaki; Mazzocco, Michele

    2013-01-01

    We propose the use of the latent change and latent acceleration frameworks for modeling nonlinear growth in structural equation models. Moving to these frameworks allows for the direct identification of "rates of change" and "acceleration" in latent growth curves--information available indirectly through traditional growth…

  5. ß-catenin, a transcription factor activated by canonical Wnt signaling, is expressed in sensory neurons of calves latently infected with bovine herpesvirus 1

    Science.gov (United States)

    Like many a-herpesvirinae subfamily members, bovine herpes virus 1 (BoHV-1) expresses an abundant transcript in latently infected sensory neurons: the latency-related (LR) RNA. LR-RNA encodes a protein (ORF2) that inhibits apoptosis, interacts with Notch family members, interferes with Notch mediate...

  6. Screening for latent tuberculous infection in people living with HIV infection in Auckland, New Zealand.

    Science.gov (United States)

    Gow, N; Briggs, S; Nisbet, M

    2017-09-01

    New Zealand, which has a low incidence of tuberculosis (TB), has historically taken a risk-based approach to screening for latent tuberculous infection (LTBI) in adult people living with the human immunodeficiency virus infection (PLHIV). To evaluate LTBI screening, treatment and outcomes in an adult PLHIV population. This was a retrospective clinical record review of an initial cohort of adult PLHIV attending the Auckland City Hospital HIV clinic in 2011, and a second cohort of adult PLHIV newly attending the clinic in 2014. We analysed high-risk (born in or acquiring HIV in a high TB incidence country) and low-risk patients using descriptive statistical methods. Of the 752 patients from the initial cohort, 416 (55%) had documentation of LTBI screening, which was positive in 74 (10%): 19/461 (4%) low-risk and 55/291 (19%) high-risk patients. LTBI treatment was received in 13 low-risk and 44 high-risk patients. Of 73 patients in the second cohort, 68 (93%) were screened. LTBI screening was incomplete in our clinic, but improved between 2011 and 2014. A significant number of patients with LTBI did not originate from a high TB incidence country.

  7. Herpesvirus papio contains a plasmid origin of replication that acts in cis interspecies with an Epstein-Barr virus trans-acting function.

    Science.gov (United States)

    Pesano, R L; Pagano, J S

    1986-01-01

    Herpesvirus papio (HVP) and Epstein-Barr virus (EBV) are closely related biologically and biochemically; lymphoblastoid cells infected with either virus contain episomal viral DNA. The putative origin of replication for EBV plasmids (oriP) has been assigned to a 1,790-base-pair fragment (cis) in the short unique region of the genome which requires a viral function supplied in trans from elsewhere in the genome (J. Yates, N. Warren, D. Reisman, and B. Sugden, Proc. Natl. Acad. Sci. USA 81:3806-3810, 1984). We report here the identification of the putative origin of replication (cis) in HVP; we assigned it to the HVP EcoRI K fragment. The results indicate that the HVP replication process requires both a cis and a trans-acting function, analogous to that found in EBV. Images PMID:3023667

  8. The origin and phylogeography of dog rabies virus

    Science.gov (United States)

    Bourhy, Hervé; Reynes, Jean-Marc; Dunham, Eleca J.; Dacheux, Laurent; Larrous, Florence; Huong, Vu Thi Que; Xu, Gelin; Yan, Jiaxin; Miranda, Mary Elizabeth G.; Holmes, Edward C.

    2012-01-01

    Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV. PMID:18931062

  9. A Protocol for Producing Virus-Free Artichoke Genetic Resources for Conservation, Breeding, and Production

    Directory of Open Access Journals (Sweden)

    Roberta Spanò

    2018-03-01

    Full Text Available The potential of the globe artichoke biodiversity in the Mediterranean area is enormous but at risk of genetic erosion because only a limited number of varieties are vegetatively propagated and grown. In Apulia (southern Italy, the Regional Government launched specific actions to rescue and preserve biodiversity of woody and vegetable crops in the framework of the Rural Development Program. Many globe artichoke ecotypes have remained neglected and unnoticed for a long time and have been progressively eroded by several causes, which include a poor phytosanitary status. Sanitation of such ecotypes from infections of vascular fungi and viruses may be a solution for their ex situ conservation and multiplication in nursery plants in conformity to the current EU Directives 93/61/CEE and 93/62/CEE that enforce nursery productions of virus-free and true-to-type certified stocks. Five Apulian ecotypes, Bianco di Taranto, Francesina, Locale di Mola, Verde di Putignano and Violetto di Putignano, were sanitized from artichoke Italian latent virus (AILV, artichoke latent virus (ArLV and tomato infectious chlorosis virus (TICV by meristem-tip culture and in vitro thermotherapy through a limited number of subcultures to reduce the risk of “pastel variants” induction of and loss of earliness. A total of 25 virus-free primary sources were obtained and conserved ex situ in a nursery.

  10. Nucleotide sequence and taxonomy of Cycas necrotic stunt virus. Brief report.

    Science.gov (United States)

    Han, S S; Karasev, A V; Ieki, H; Iwanami, T

    2002-11-01

    Cycas necrotic stunt virus (CNSV) is the only well-characterized virus from gymnosperm. cDNA segments corresponding to the bipartite genome RNAs (RNA1, RNA2) were synthesized and sequenced. Each RNA encoded a single polyprotein, flanked by the 5' and 3' non-coding regions (NCR) and followed by a poly (A) tail. The putative polyproteins encoded by RNA1 and RNA2 had sets of motifs, which were characteristic of viruses in the genus Nepovirus. The polyproteins showed higher sequence identities to Artichoke Italian latent virus, Grapevine chrome mosaic virus and Tomato black ring virus, all of which belong to subgroup b of the genus Nepovirus, than to other nepoviruses. Phylogenetic analysis of RNA dependent RNA polymerase and coat protein also showed closer relationships with these viruses than other viruses. The data obtained supported the taxonomical status of CNSV as a definitive member of the genus Nepovirus, subgroup b.

  11. Dual expression of Epstein-Barr virus, latent membrane protein-1 and human papillomavirus-16 E6 transform primary mouse embryonic fibroblasts through NF-κB signaling.

    Science.gov (United States)

    Shimabuku, Tetsuya; Tamanaha, Ayumi; Kitamura, Bunta; Tanabe, Yasuka; Tawata, Natsumi; Ikehara, Fukino; Arakaki, Kazunari; Kinjo, Takao

    2014-01-01

    The prevalence of Epstein-Barr virus (EBV) and high-risk human papilloma virus (HPV) infections in patients with oral cancer in Okinawa, southwest islands of Japan, has led to the hypothesis that carcinogenesis is related to EBV and HPV co-infection. To explore the mechanisms of transformation induced by EBV and HPV co-infection, we analyzed the transformation of primary mouse embryonic fibroblasts (MEFs) expressing EBV and HPV-16 genes, alone or in combination. Expression of EBV latent membrane protein-1 (LMP-1) alone or in combination with HPV-16 E6 increased cell proliferation and decreased apoptosis, whereas single expression of EBV nuclear antigen-1 (EBNA-1), or HPV-16 E6 did not. Co-expression of LMP-1 and E6 induced anchorage-independent growth and tumor formation in nude mice, whereas expression of LMP-1 alone did not. Although the singular expression of these viral genes showed increased DNA damage and DNA damage response (DDR), co-expression of LMP-1 and E6 did not induce DDR, which is frequently seen in cancer cells. Furthermore, co-expression of LMP-1 with E6 increased NF-κB signaling, and the knockdown of LMP-1 or E6 in co-expressing cells decreased cell proliferation, anchorage independent growth, and NF-κB activation. These data suggested that expression of individual viral genes is insufficient for inducing transformation and that co-expression of LMP-1 and E6, which is associated with suppression of DDR and increased NF-κB activity, lead to transformation. Our findings demonstrate the synergistic effect by the interaction of oncogenes from different viruses on the transformation of primary MEFs.

  12. Varicella zoster virus vaccines: potential complications and possible improvements.

    Science.gov (United States)

    Silver, Benjamin; Zhu, Hua

    2014-10-01

    Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

  13. The New Report of Artichoke latent virus (ArLV) From Globe Artichoke in Turkey

    OpenAIRE

    ERKAN, Semih; GÜMÜŞ, Mustafa; DUMAN, İbrahim; PAYLAN, İsmail Can; ERGÜN, Müge

    2014-01-01

    n recent years, some of artichoke growers in Aegean region of Turkey stated that globe artichoke (Cynara cardunculus L. subsp. scolymus (L.) Hayek) plants in their fields have showed virus-like symptoms. So, in order to identify viruses

  14. Limited Antigenic Diversity in Contemporary H7 Avian-Origin Influenza A Viruses from North America

    Science.gov (United States)

    Xu, Yifei; Bailey, Elizabeth; Spackman, Erica; Li, Tao; Wang, Hui; Long, Li-Ping; Baroch, John A.; Cunningham, Fred L.; Lin, Xiaoxu; Jarman, Richard G.; DeLiberto, Thomas J.; Wan, Xiu-Feng

    2016-01-01

    Subtype H7 avian–origin influenza A viruses (AIVs) have caused at least 500 confirmed human infections since 2003 and culling of >75 million birds in recent years. Here we antigenically and genetically characterized 93 AIV isolates from North America (85 from migratory waterfowl [1976–2010], 7 from domestic poultry [1971–2012], and 1 from a seal [1980]). The hemagglutinin gene of these H7 viruses are separated from those from Eurasia. Gradual accumulation of nucleotide and amino acid substitutions was observed in the hemagglutinin of H7 AIVs from waterfowl and domestic poultry. Genotype characterization suggested that H7 AIVs in wild birds form diverse and transient internal gene constellations. Serologic analyses showed that the 93 isolates cross-reacted with each other to different extents. Antigenic cartography showed that the average antigenic distance among them was 1.14 units (standard deviation [SD], 0.57 unit) and that antigenic diversity among the H7 isolates we tested was limited. Our results suggest that the continuous genetic evolution has not led to significant antigenic diversity for H7 AIVs from North America. These findings add to our understanding of the natural history of IAVs and will inform public health decision-making regarding the threat these viruses pose to humans and poultry. PMID:26858078

  15. Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

    Directory of Open Access Journals (Sweden)

    Nathalie Alazard-Dany

    2009-03-01

    Full Text Available The human parvovirus Adeno-Associated Virus (AAV type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1; whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/primase (HP complex (UL5/8/52 and the single-stranded DNA-Binding Protein (ICP8 were sufficient to induce AAV-2 replication in transfected cells. We independently showed that, in the context of a latent AAV-2 infection, the HSV-1 ICP0 protein was able to activate rep gene expression. The present study was conducted to integrate these observations and to further explore the requirement of other HSV-1 proteins during early AAV replication steps, i.e. rep gene expression and AAV DNA replication. Using a cellular model that mimics AAV latency and composite constructs coding for various sets of HSV-1 genes, we first confirmed the role of ICP0 for rep gene expression and demonstrated a synergistic effect of ICP4 and, to a lesser extent, ICP22. Conversely, ICP27 displayed an inhibitory effect. Second, our analyses showed that the effect of ICP0, ICP4, and ICP22 on rep gene expression was essential for the onset of AAV DNA replication in conjunction with the HP complex and ICP8. Third, and most importantly, we demonstrated that the HSV-1 DNA polymerase complex (UL30/UL42 was critical to enhance AAV DNA replication to a significant level in transfected cells and that its catalytic activity was involved in this process. Altogether, this work represents the first comprehensive study recapitulating the series of early events taking place during HSV-1-induced AAV replication.

  16. Spectrum of Epstein-Barr virus-related diseases. A pictorial review

    International Nuclear Information System (INIS)

    Maeda, Eriko; Akahane, Masaaki; Kiryu, Shigeru

    2009-01-01

    Epstein-Barr virus (EBV) prevails among more than 90% of the adult population worldwide. Most primary infections occur during young childhood and cause no or only nonspecific symptoms; then the virus becomes latent and resides in lymphocytes in the peripheral blood. Inactive latent EBV usually causes no serious consequences, but once it becomes active it can cause a wide spectrum of malignancies: epithelial tumors such as nasopharyngeal and gastric carcinomas; mesenchymal tumors such as follicular dendritic cell tumor/sarcoma; and lymphoid malignancies such as Burkitt lymphoma, lymphomatoid granulomatosis, pyothorax-associated lymphoma, immunodeficiency-associated lymphoproliferative disorders, extranodal natural killer (NK) cell/T-cell lymphoma, and Hodgkin's lymphoma. The purpose of this article is to describe the spectrum of EBV-related diseases and their key imaging findings. EBV-related lymphoproliferative disorders and lymphomas are especially common in immunocompromised patients. Awareness of their clinical settings and imaging spectrum contributes to early detection and early treatment of possibly life-threatening disorders. (author)

  17. Evolutionary origins of hepatitis A virus in small mammals

    NARCIS (Netherlands)

    J.-F. Drexler (Jan-Felix); V.M. Corman (Victor); A.N. Lukashev (Alexander); J.M.A. van den Brand (Judith); A. Gmyl (Anatoly); S. Brunink (Sebastian); A. Rasche (Andrea); N. Seggewi (Nicole); H. Feng (Hui); L.M.E. Leijten (Lonneke); P. Vallo (Peter); T. Kuiken (Thijs); A. Dotzauer (Andreas); R.G. Ulrich (Rainer); S.M. Lemon (Stanley M.); C. Drosten (Christian)

    2015-01-01

    textabstractHepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian

  18. Longitudinal Research with Latent Variables

    CERN Document Server

    van Montfort, Kees; Satorra, Albert

    2010-01-01

    This book combines longitudinal research and latent variable research, i.e. it explains how longitudinal studies with objectives formulated in terms of latent variables should be carried out, with an emphasis on detailing how the methods are applied. Because longitudinal research with latent variables currently utilizes different approaches with different histories, different types of research questions, and different computer programs to perform the analysis, the book is divided into nine chapters. Starting from some background information about the specific approach, short history and the ma

  19. The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.

    Science.gov (United States)

    Xu, Lili; Bao, Linlin; Deng, Wei; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Yong, Weidong; Wei, Qiang; Zhang, Lianfeng; Qin, Chuan

    2013-08-08

    The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus. A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3-5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models. The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

  20. Latency in vitro using irradiated Herpes simplex virus

    International Nuclear Information System (INIS)

    Nishiyama, Y.; Rapp, F.

    1981-01-01

    Human embryonic fibroblasts infected with u.v.-irradiated herpes simplex virus type 2 (HSV-2, strain 186) and maintained at 40.5 0 C did not yield detectable virus. Virus synthesis was induced by temperature shift-down to 36.5 0 C. The induced virus grew very poorly and was inactivated very rapidly at 40.5 0 C. Non-irradiated virus failed to establish latency at 40.5 0 C in infected cells. Enhanced reactivation of HSV-2 was observed when latently infected cultures were superinfected with human cytomegalovirus (HCMV) or irradiated with a small dose of u.v. light at the time of temperature shift-down. HCMV did not enhance synthesis of HSV-2 during a normal growth cycle but did enhance synthesis of u.v.-irradiated HSV-2. These observations suggest that in this in vitro latency system, some HSV genomes damaged by u.v. irradiation were maintained in a non-replicating state without being destroyed or significantly repaired. (author)

  1. Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections.

    Science.gov (United States)

    O'Bryan, Joel M; Woda, Marcia; Co, Mary; Mathew, Anuja; Rothman, Alan L

    2013-08-26

    Declining telomere length (TL) is associated with T cell senescence. While TL in naïve and memory T cells declines with increasing age, there is limited data on TL dynamics in virus-specific memory CD4+ T cells in healthy adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL in T cells specific for several virus infections: non-recurring acute (vaccinia virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects. Additionally, five subjects provided multiple blood samples separated by up to 10 years. VACV- and CMV-specific T cells had longer average TL than IAV-specific CD4+ T cells. Although most virus-specific cells were CD45RA-, we observed a minor population of BrdU+ CD45RA+ T cells characterized by long telomeres. Longitudinal analysis demonstrated a slow decline in average TL in virus-specific T cells. However, in one subject, VZV reactivation led to an increase in average TL in VZV-specific memory T cells, suggesting a conversion of longer TL cells from the naïve T cell repertoire. TLs in memory CD4+ T cells in otherwise healthy adults are heterogeneous and follow distinct virus-specific kinetics. These findings suggests that the distribution of TL and the creation and maintenance of long TL memory T cells could be important for the persistence of long-lived T cell memory.

  2. Latent Autoimmune Diabetes of the Adult (LADA in a Brazilian Indian

    Directory of Open Access Journals (Sweden)

    João Paulo Botelho Vieira Filho

    Full Text Available CONTEXT: Latent autoimmune diabetes of the adult (LADA as originally described represents perhaps as many as 10 -- 20% of adult-onset patients with diabetes. DESIGN: case report. CASE REPORT: A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.

  3. Experimental infection of duck origin virulent Newcastle disease virus strain in ducks.

    Science.gov (United States)

    Dai, Yabin; Cheng, Xu; Liu, Mei; Shen, Xinyue; Li, Jianmei; Yu, Shengqing; Zou, Jianmin; Ding, Chan

    2014-07-17

    Newcastle disease (ND) caused by virulent Newcastle disease virus (NDV) is an acute, highly contagious and fatal viral disease affecting most species of birds. Ducks are generally considered to be natural reservoirs or carriers of NDV while being resistant to NDV strains, even those most virulent for chickens; however, natural ND cases in ducks have been gradually increasing in recent years. In the present study, ducks of different breeds and ages were experimentally infected with duck origin virulent NDV strain duck/Jiangsu/JSD0812/2008 (JSD0812) by various routes to investigate the pathogenicity of NDV in ducks. Six breeds (mallard, Gaoyou, Shaoxing, Jinding, Shanma, and Pekin ducks) were infected intramuscularly (IM) with JSD0812 strain at the dose of 5 × 108 ELD50. Susceptibility to NDV infection among breeds varied, per morbidity and mortality. Mallard ducks were the most susceptible, and Pekin ducks the most resistant. Fifteen-, 30-, 45-, 60-, and 110-day-old Gaoyou ducks were infected with JSD0812 strain at the dose of 5 × 108 ELD50 either IM or intranasally (IN) and intraocularly (IO), and their disease development, viral shedding, and virus tissue distribution were determined. The susceptibility of ducks to NDV infection decreased with age. Most deaths occurred in 15- and 30-day-old ducklings infected IM. Ducks infected IN and IO sometimes exhibited clinical signs, but seldom died. Clinical signs were primarily neurologic. Infected ducks could excrete infectious virus from the pharynx and/or cloaca for a short period, which varied with bird age or inoculation route; the longest period was about 7 days. The rate of virus isolation in tissues from infected ducks was generally low, even in those from dead birds, and it appeared to be unrelated to bird age and infection route. The results confirmed that some of the naturally occurring NDV virulent strains can cause the disease in ducks, and that ducks play an important role in the epidemiology of ND. The

  4. The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus

    International Nuclear Information System (INIS)

    Kutz, Helmut; Reisbach, Gilbert; Schultheiss, Ute; Kieser, Arnd

    2008-01-01

    The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) transforms cells activating signal transduction pathways such as NF-κB, PI3-kinase, or c-Jun N-terminal kinase (JNK). Here, we investigated the functional role of the LMP1-induced JNK pathway in cell transformation. Expression of a novel dominant-negative JNK1 allele caused a block of proliferation in LMP1-transformed Rat1 fibroblasts. The JNK-specific inhibitor SP600125 reproduced this effect in Rat1-LMP1 cells and efficiently interfered with proliferation of EBV-transformed lymphoblastoid cells (LCLs). Inhibition of the LMP1-induced JNK pathway in LCLs caused the downregulation of c-Jun and Cdc2, the essential G2/M cell cycle kinase, which was accompanied by a cell cycle arrest of LCLs at G2/M phase transition. Moreover, SP600125 retarded tumor growth of LCLs in a xenograft model in SCID mice. Our data support a critical role of the LMP1-induced JNK pathway for proliferation of LMP1-transformed cells and characterize JNK as a potential target for intervention against EBV-induced malignancies

  5. Diagnóstico y clasificación molecular del virus BK en receptores de trasplante renal

    OpenAIRE

    Riva, Omar; Cobos, Marisa; Raimondi, J. Clemente

    2010-01-01

    La infección primaria por virus BK ocurre durante la infancia permaneciendo latente en el tracto urogenital. En individuos que presentan alteraciones en la inmunidad celular, el virus se reactiva haciendo posible su detección en orina y sangre. En receptores de trasplante renal, la nefropatía producida por el virus BK puede llevar a la pérdida de la función del injerto. El virus BK es miembro de la familia Polyomaviridae, presenta un genoma de ADN circular doble cadena unido en forma covalent...

  6. Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

    Science.gov (United States)

    Choudhury, Vivek; Amin, Sanjiv B; Agarwal, Asha; Srivastava, L M; Soni, Arun; Saluja, Satish

    2015-11-01

    In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score 75 ng/mL) at birth. Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397. © 2015 American Society for Nutrition.

  7. Interplay of viruses and radiation in carcinogenesis

    International Nuclear Information System (INIS)

    Upton, A.C.

    1975-01-01

    The discovery by Gross and by Lieberman and Kaplan that leukemias induced by irradiation in mice may be transmissible by cell-free filtrates pointed to the existence of an interplay between the effects of radiation and those of an otherwise latent oncogenic virus, which has since been the subject of intensive study. In the years intervening since these pioneer observations, efforts have been made to elucidate the nature and mechanisms of the interplay and to determine whether other neoplasms also may be elicited by an interaction between virus and radiation. The results of these efforts, although still highly preliminary, are surveyed in the light of recent advances in viral oncology

  8. Viruses & kidney disease: beyond HIV

    OpenAIRE

    Waldman, Meryl; Marshall, Vickie; Whitby, Denise; Kopp, Jeffrey B.

    2008-01-01

    HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and t...

  9. Cytomegalovirus establishes a latent reservoir and triggers long-lasting inflammation in the eye.

    Directory of Open Access Journals (Sweden)

    Valentina Voigt

    2018-05-01

    Full Text Available Recent outbreaks of Ebola and Zika have highlighted the possibility that viruses may cause enduring infections in tissues like the eye, including the neural retina, which have been considered immune privileged. Whether this is a peculiarity of exotic viruses remains unclear, since the impact of more common viral infections on neural compartments has not been examined, especially in immunocompetent hosts. Cytomegalovirus is a common, universally distributed pathogen, generally innocuous in healthy individuals. Whether in immunocompetent hosts cytomegalovirus can access the eye, and reside there indefinitely, was unknown. Using the well-established murine cytomegalovirus infection model, we show that systemic infection of immunocompetent hosts results in broad ocular infection, chronic inflammation and establishment of a latent viral pool in the eye. Infection leads to infiltration and accumulation of anti-viral CD8+ T cells in the eye, and to the development of tissue resident memory T cells that localize to the eye, including the retina. These findings identify the eye as an unexpected reservoir for cytomegalovirus, and suggest that common viruses may target this organ more frequently than appreciated. Notably, they also highlight that infection triggers sustained inflammatory responses in the eye, including the neural retina.

  10. Effect of Raspberry bushy dwarf virus, Raspberry leaf mottle virus, and Raspberry latent virus on plant growth and fruit crumbliness in ‘Meeker’ red Raspberry

    Science.gov (United States)

    Raspberry crumbly fruit in red raspberry (Rubus idaeus L.), widespread in the Pacific Northwest of the United States and British Columbia, Canada, is most commonly caused by a virus infection. Raspberry bushy dwarf virus (RBDV) has long been attributed as the causal agent of the disease. Recently, t...

  11. Exosomes released in vitro from Epstein-Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs.

    Science.gov (United States)

    Canitano, Andrea; Venturi, Giulietta; Borghi, Martina; Ammendolia, Maria Grazia; Fais, Stefano

    2013-09-01

    EBV is a human herpesvirus associated with a number of malignancies. Both lymphoblastoid cell lines (LCLs), and EBV-infected nasopharyngeal carcinoma (NPC) cells have been demonstrated to release exosomes containing the EBV-encoded latent membrane protein 1 (LMP1), and mature micro-RNAs (EBV-miRNAs). Here we analyze the EBV protein and nucleic acid content of exosomes from different EBV-infected cells (LCL, 721 and Daudi) and we show for the first time that exosomes released from LCLs and 721 also contain EBV-encoded latent phase mRNAs. This confirms and strengthens exosomes pathogenetic potential, and might provide insights for development of novel diagnostic and therapeutic strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. High-sensitivity virus and mycoplasma screening test reveals high prevalence of parvovirus B19 infection in human synovial tissues and bone marrow.

    Science.gov (United States)

    Watanabe, Ken; Otabe, Koji; Shimizu, Norio; Komori, Keiichirou; Mizuno, Mitsuru; Katano, Hisako; Koga, Hideyuki; Sekiya, Ichiro

    2018-03-27

    Latent microorganism infection is a safety concern for the clinical application of mesenchymal stem cells (MSCs). The aim of this study is to investigate the frequencies and sensitivities of the latent virus and mycoplasma infections in synovium, bone marrow, peripheral blood cells, and blood plasma and cultured synovial MSCs. Total DNA and RNA of the synovium (n = 124), bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14-day cultured synovial MSCs (n = 63) were collected from patients who underwent total knee arthroplasty or anterior ligament reconstruction after written informed consents were obtained. The multiplex polymerase chain reaction (PCR) primers were designed to quantitatively measure the representative genomes of 13 DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and virus spike test were also performed to demonstrate the sensitivity of synovial MSCs to the candidate pathogens. In synovium and bone marrow, the positive rates of parvovirus B19 genome were significantly higher than in peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment analysis of amplified and sequenced viral target genes showed the proximity of the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs cultured for 14 days were positive for virus infection only in two patients (2/62 = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples. Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. This study revealed a relatively high incidence of latent parvovirus B19 in synovium and bone marrow tissue.

  13. Computer Viruses: Pathology and Detection.

    Science.gov (United States)

    Maxwell, John R.; Lamon, William E.

    1992-01-01

    Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

  14. Detecting New Words from Chinese Text Using Latent Semi-CRF Models

    Science.gov (United States)

    Sun, Xiao; Huang, Degen; Ren, Fuji

    Chinese new words and their part-of-speech (POS) are particularly problematic in Chinese natural language processing. With the fast development of internet and information technology, it is impossible to get a complete system dictionary for Chinese natural language processing, as new words out of the basic system dictionary are always being created. A latent semi-CRF model, which combines the strengths of LDCRF (Latent-Dynamic Conditional Random Field) and semi-CRF, is proposed to detect the new words together with their POS synchronously regardless of the types of the new words from the Chinese text without being pre-segmented. Unlike the original semi-CRF, the LDCRF is applied to generate the candidate entities for training and testing the latent semi-CRF, which accelerates the training speed and decreases the computation cost. The complexity of the latent semi-CRF could be further adjusted by tuning the number of hidden variables in LDCRF and the number of the candidate entities from the Nbest outputs of the LDCRF. A new-words-generating framework is proposed for model training and testing, under which the definitions and distributions of the new words conform to the ones existing in real text. Specific features called “Global Fragment Information” for new word detection and POS tagging are adopted in the model training and testing. The experimental results show that the proposed method is capable of detecting even low frequency new words together with their POS tags. The proposed model is found to be performing competitively with the state-of-the-art models presented.

  15. Development of a Vaccine Incorporating Killed Virus of Canine Origin for the Prevention of Canine Parvovirus Infection

    OpenAIRE

    Povey, C.

    1982-01-01

    A parvovirus of canine origin, cultured in a feline kidney cell line, was inactivated with formalin. Three pilot serials were produced and three forms of finished vaccine (nonadjuvanted, single adjuvanted and double adjuvanted) were tested in vaccination and challenge trials. A comparison was also made with two inactivated feline panleukopenia virus vaccines, one of which has official approval for use in dogs. The inactivated canine vaccine in nonadjuvanted, adjuvanted or double adjuvanted fo...

  16. [The great virus comeback].

    Science.gov (United States)

    Forterre, Patrick

    2013-01-01

    Viruses have been considered for a long time as by-products of biological evolution. This view is changing now as a result of several recent discoveries. Viral ecologists have shown that viral particles are the most abundant biological entities on our planet, whereas metagenomic analyses have revealed an unexpected abundance and diversity of viral genes in the biosphere. Comparative genomics have highlighted the uniqueness of viral sequences, in contradiction with the traditional view of viruses as pickpockets of cellular genes. On the contrary, cellular genomes, especially eukaryotic ones, turned out to be full of genes derived from viruses or related elements (plasmids, transposons, retroelements and so on). The discovery of unusual viruses infecting archaea has shown that the viral world is much more diverse than previously thought, ruining the traditional dichotomy between bacteriophages and viruses. Finally, the discovery of giant viruses has blurred the traditional image of viruses as small entities. Furthermore, essential clues on virus history have been obtained in the last ten years. In particular, structural analyses of capsid proteins have uncovered deeply rooted homologies between viruses infecting different cellular domains, suggesting that viruses originated before the last universal common ancestor (LUCA). These studies have shown that several lineages of viruses originated independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses have coevolved with their hosts, and viral lineages can be viewed as lianas wrapping around the trunk, branches and leaves of the tree of life. Although viruses are very diverse, with genomes encoding from one to more than one thousand proteins, they can all be simply defined as organisms producing virions. Virions themselves can be defined as infectious particles made of at least one protein associated with the viral nucleic acid, endowed with the capability to protect the viral genome and ensure its

  17. Influenza A viruses of avian origin circulating in pigs and other mammals.

    Science.gov (United States)

    Urbaniak, Kinga; Kowalczyk, Andrzej; Markowska-Daniel, Iwona

    2014-01-01

    Influenza A viruses (IAVs) are zoonotic agents, capable of crossing the species barriers. Nowadays, they still constitute a great challenge worldwide. The natural reservoir of all influenza A viruses are wild aquatic birds, despite the fact they have been isolated from a number of avian and mammalian species, including humans. Even when influenza A viruses are able to get into another than waterfowl population, they are often unable to efficiently adapt and transmit between individuals. Only in rare cases, these viruses are capable of establishing a new lineage. To succeed a complete adaptation and further transmission between species, influenza A virus must overcome a species barrier, including adaptation to the receptors of a new host, which would allow the virus-cell binding, virus replication and, then, animal-to-animal transmission. For many years, pigs were thought to be intermediate host for adaptation of avian influenza viruses to humans, because of their susceptibility to infection with both, avian and human influenza viruses, which supported hypothesis of pigs as a 'mixing vessel'. In this review, the molecular factors necessary for interspecies transmission are described, with special emphasis on adaptation of avian influenza viruses to the pig population. In addition, this review gives the information about swine influenza viruses circulating around the world with special emphasis on Polish strains.

  18. Distribution of herpes simplex virus types 1 and 2 genomes in human spinal ganglia studied by PCR and in situ hybridization.

    Science.gov (United States)

    Obara, Y; Furuta, Y; Takasu, T; Suzuki, S; Suzuki, H; Matsukawa, S; Fujioka, Y; Takahashi, H; Kurata, T; Nagashima, K

    1997-06-01

    Clinical data indicate that the recurring herpes simplex virus (HSV) from oro-labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV-2. This suggests that HSV-1 and HSV-2 reside in latent forms in the trigeminal ganglia and sacral ganglia, respectively. However, the distribution of latent HSV-1 and HSV-2 infections in human spinal ganglia has not been fully examined. This report concerns the application of polymerase chain reaction (PCR) and in situ hybridization (ISH) to such a study. By using PCR and employing the respective primers, HSV-1 and HSV-2 DNAs were detected in 207 of 524 samples from 262 spinal ganglia (from the cervical to the sacral ganglia) examined on both sides. The percentages of HSV-1 and HSV-2 detected in a given set of ganglia were similar, indicating an absence of site preference. By ISH, few but positive hybridization signals were detected evenly in sacral ganglia sections. The data suggest that regional specificity of recurrent HSV infections is not due to regional distribution of latent virus, but that local host factors may be important for recurrences.

  19. Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

    International Nuclear Information System (INIS)

    Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan; Lynn, Annie; Cotmore, Susan F.; Tattersall, Peter; Zhao, Haiyan; Tang, Liang

    2015-01-01

    Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase active site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication

  20. Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

    Energy Technology Data Exchange (ETDEWEB)

    Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan; Lynn, Annie [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States); Cotmore, Susan F. [Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510 (United States); Tattersall, Peter [Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510 (United States); Departments of Genetics, Yale University Medical School, New Haven, CT 06510 (United States); Zhao, Haiyan, E-mail: zhaohy@ku.edu [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States); Tang, Liang, E-mail: tangl@ku.edu [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States)

    2015-02-15

    Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase active site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication.

  1. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired...

  2. Modeling conductive heat transfer during high-pressure thawing processes: determination of latent heat as a function of pressure.

    Science.gov (United States)

    Denys, S; Van Loey, A M; Hendrickx, M E

    2000-01-01

    A numerical heat transfer model for predicting product temperature profiles during high-pressure thawing processes was recently proposed by the authors. In the present work, the predictive capacity of the model was considerably improved by taking into account the pressure dependence of the latent heat of the product that was used (Tylose). The effect of pressure on the latent heat of Tylose was experimentally determined by a series of freezing experiments conducted at different pressure levels. By combining a numerical heat transfer model for freezing processes with a least sum of squares optimization procedure, the corresponding latent heat at each pressure level was estimated, and the obtained pressure relation was incorporated in the original high-pressure thawing model. Excellent agreement with the experimental temperature profiles for both high-pressure freezing and thawing was observed.

  3. Cocoa swollen shoot virus in Ghana: A review of diagnostic ...

    African Journals Online (AJOL)

    A quick and more reliable diagnostic method has for a long time been identified as one input that will greatly enhance the control of the cocoa swollen shoot disease in Ghana. Many diagnostic procedures have been developed for detecting the virus that causes the disease; yet, the detection of latent infections is still ...

  4. Herpes simplex-virus type 1 påvist hos patient med herpes zoster

    DEFF Research Database (Denmark)

    Danielsen, Patricia Louise; Schønning, Kristian; Larsen, Helle Kiellberg

    2012-01-01

    In this case report we present an otherwise healthy 63 year-old male patient with herpes zoster corresponding to the 2nd left branch of the trigeminal nerve. Real time-polymerase chain reaction analyses were positive for both herpes simplex virus (HSV) type 1 and varicella zoster virus (VZV......). The most probable explanation is that this reflects asymptomatic, latent expression of HSV-1 in a herpes zoster patient with no clinical relevance. Another hypothesis is that reactivation of a neurotropic herpes virus can reactivate another neurotropic virus if both types are present in the same ganglion....... If co-infection with HSV/VZV is suspected the treatment regimen for herpes zoster will sufficiently treat a possible HSV infection also....

  5. Carcinoma-risk variant of EBNA1 deregulates Epstein-Barr Virus episomal latency.

    Science.gov (United States)

    Dheekollu, Jayaraju; Malecka, Kimberly; Wiedmer, Andreas; Delecluse, Henri-Jacques; Chiang, Alan K S; Altieri, Dario C; Messick, Troy E; Lieberman, Paul M

    2017-01-31

    Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection. We identify Survivin as a host protein deficiently bound by the NPC variant of EBNA1 and show that Survivin depletion compromises EBV episome maintenance in multiple cell types. We propose that endemic variants of EBNA1 play a significant role in EBV-driven carcinogenesis by altering key regulatory interactions that destabilize latent infection.

  6. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

    Science.gov (United States)

    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  7. Examining the hemagglutinin subtype diversity among wild duck-origin influenza A viruses using ethanol-fixed cloacal swabs and a novel RT-PCR method.

    Science.gov (United States)

    Wang, Ruixue; Soll, Lindsey; Dugan, Vivien; Runstadler, Jonathan; Happ, George; Slemons, Richard D; Taubenberger, Jeffery K

    2008-05-25

    This study presents an interconnected approach for circumventing two inherent limitations associated with studies defining the natural history of influenza A viruses in wild birds. The first limiting factor is the ability to maintain a cold chain from specimen collection to the laboratory when study sites are in more remote locations. The second limiting factor is the ability to identify all influenza A virus HA subtypes present in an original sample. We report a novel method for molecular subtyping of avian influenza A virus hemagglutinin genes using degenerate primers designed to amplify all known hemagglutinin subtypes. It was shown previously that templates larger than 200 bp were not consistently amplifiable from ethanol-fixed cloacal swabs. For this study, new primer sets were designed within these constraints. This method was used to perform subtyping RT-PCR on 191 influenza RNA-positive ethanol-fixed cloacal swabs obtained from 880 wild ducks in central Alaska in 2005. Seven different co-circulating hemagglutinin subtypes were identified in this study set, including H1, H3, H4, H5, H6, H8, and H12. In addition, 16% of original cloacal samples showed evidence of mixed infection, with samples yielding from two-to-five different hemagglutinin subtypes. This study further demonstrates the complex ecobiology of avian influenza A viruses in wild birds.

  8. Stability of latent class segments over time

    DEFF Research Database (Denmark)

    Mueller, Simone

    2011-01-01

    Dynamic stability, as the degree to which identified segments at a given time remain unchanged over time in terms of number, size and profile, is a desirable segment property which has received limited attention so far. This study addresses the question to what degree latent classes identified from...... logit model suggests significant changes in the price sensitivity and the utility from environmental claims between both experimental waves. A pooled scale adjusted latent class model is estimated jointly over both waves and the relative size of latent classes is compared across waves, resulting...... in significant differences in the size of two out of seven classes. These differences can largely be accounted for by the changes on the aggregated level. The relative size of latent classes is correlated at 0.52, suggesting a fair robustness. An ex-post characterisation of latent classes by behavioural...

  9. Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus Episome Maintenance.

    Science.gov (United States)

    Deakyne, Julianna S; Malecka, Kimberly A; Messick, Troy E; Lieberman, Paul M

    2017-10-01

    Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome, but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher-order EBNA1 complexes. Substitution mutations around the interface destabilized higher-order complex formation and altered the cooperative DNA-binding properties of EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance with OriP. We found that one naturally occurring polymorphism in the oligomer interface (T585P) had greater cooperative DNA binding in vitro , minor defects in DNA replication, and pronounced defects in episome maintenance. The T585P mutant was compromised for binding to OriP in vivo as well as for assembling the origin recognition complex subunit 2 (ORC2) and trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also compromised for forming stable subnuclear foci in living cells. These findings reveal a novel oligomeric structure of EBNA1 with an interface subject to naturally occurring polymorphisms that modulate EBNA1 functional properties. We propose that EBNA1 dimers can assemble into higher-order oligomeric structures important for diverse functions of EBNA1. IMPORTANCE Epstein-Barr virus is a human gammaherpesvirus that is causally associated with various cancers. Carcinogenic properties are linked to the ability of the virus to persist in the latent form for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein that is consistently expressed in EBV tumors and is the only viral protein required to maintain the viral

  10. Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure.

    Science.gov (United States)

    George, Jeffy; Mattapallil, Joseph J

    2018-01-01

    Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus. Interferon-α (IFN-α) is an innate cytokine that has been shown to activate intracellular defenses capable of restricting and controlling HIV. IFN-α, however, harbors numerous functional subtypes that have been reported to display different binding affinities and potency. Recent studies have suggested that certain subtypes such as IFN-α8 and IFN-α14 have potent anti-HIV activity with little or no immune activation, whereas other subtypes such as IFN-α4, IFN-α5, and IFN-α14 activate NK cells. Could these subtypes be used in combination with other strategies to reduce the latent viral reservoir? Here, we review the role of IFN-α subtypes in HIV infection and discuss the possibility that certain subtypes could be potential adjuncts to a "shock and kill" or therapeutic vaccination strategy leading to better control of the latent reservoir and subsequent functional cure.

  11. Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases.

    Science.gov (United States)

    Niller, Hans Helmut; Banati, Ferenc; Salamon, Daniel; Minarovits, Janos

    2016-01-01

    Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific "epigenetic signature". Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.

  12. Radioimmunoassay for herpes simplex virus (HSV) thymidine kinase

    International Nuclear Information System (INIS)

    McGuirt, P.V.; Keller, P.M.; Elion, G.B.

    1982-01-01

    A sensitive RIA for HSV-1 thymidine kinase (TK) has been developed. This assay is based on competition for the binding site of a rabbit antibody against purified HSV-1 TK, between a purified 3 H-labeled HSV-1 TK and a sample containing an unknown amount of viral TK. The assay is capable of detecting 8 ng or more of the HSV enzyme. Purified HSV-1 TK denatured to <1% of its original kinase activity is as effective in binding to the antibody as is native HSV-1 TK. Viral TK is detectable at ranges of 150-460 ng/mg protein of cell extract from infected cells or cells transformed by HSV or HSV genetic material. HSV-2 TK appears highly cross-reactive, VZV TK is slightly less so, and the vaccinia TK shows little or no cross-reactivity. This RIA may serve as a tool for monitoring the expression of the HSV TK during an active herpes virus infection, a latent ganglionic infection, or in neoplastic cells which may have arisen by viral transformation

  13. Immune Evasion by Epstein-Barr Virus.

    Science.gov (United States)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, Emmanuel J H J

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

  14. AN MHC class I immune evasion gene of Marek's disease virus

    Science.gov (United States)

    Marek's disease virus (MDV) is a widespread a-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198–205 (2001)), but the gene(s) involved have not been identified. Here...

  15. Machine-assisted verification of latent fingerprints: first results for nondestructive contact-less optical acquisition techniques with a CWL sensor

    Science.gov (United States)

    Hildebrandt, Mario; Kiltz, Stefan; Krapyvskyy, Dmytro; Dittmann, Jana; Vielhauer, Claus; Leich, Marcus

    2011-11-01

    A machine-assisted analysis of traces from crime scenes might be possible with the advent of new high-resolution non-destructive contact-less acquisition techniques for latent fingerprints. This requires reliable techniques for the automatic extraction of fingerprint features from latent and exemplar fingerprints for matching purposes using pattern recognition approaches. Therefore, we evaluate the NIST Biometric Image Software for the feature extraction and verification of contact-lessly acquired latent fingerprints to determine potential error rates. Our exemplary test setup includes 30 latent fingerprints from 5 people in two test sets that are acquired from different surfaces using a chromatic white light sensor. The first test set includes 20 fingerprints on two different surfaces. It is used to determine the feature extraction performance. The second test set includes one latent fingerprint on 10 different surfaces and an exemplar fingerprint to determine the verification performance. This utilized sensing technique does not require a physical or chemical visibility enhancement of the fingerprint residue, thus the original trace remains unaltered for further investigations. No particular feature extraction and verification techniques have been applied to such data, yet. Hence, we see the need for appropriate algorithms that are suitable to support forensic investigations.

  16. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  17. A Probabilistic Recommendation Method Inspired by Latent Dirichlet Allocation Model

    Directory of Open Access Journals (Sweden)

    WenBo Xie

    2014-01-01

    Full Text Available The recent decade has witnessed an increasing popularity of recommendation systems, which help users acquire relevant knowledge, commodities, and services from an overwhelming information ocean on the Internet. Latent Dirichlet Allocation (LDA, originally presented as a graphical model for text topic discovery, now has found its application in many other disciplines. In this paper, we propose an LDA-inspired probabilistic recommendation method by taking the user-item collecting behavior as a two-step process: every user first becomes a member of one latent user-group at a certain probability and each user-group will then collect various items with different probabilities. Gibbs sampling is employed to approximate all the probabilities in the two-step process. The experiment results on three real-world data sets MovieLens, Netflix, and Last.fm show that our method exhibits a competitive performance on precision, coverage, and diversity in comparison with the other four typical recommendation methods. Moreover, we present an approximate strategy to reduce the computing complexity of our method with a slight degradation of the performance.

  18. UNSOLVED AND LATENT CRIME: DIFFERENCES AND SIMILARITIES

    Directory of Open Access Journals (Sweden)

    Mikhail Kleymenov

    2017-01-01

    Full Text Available УДК 343Purpose of the article is to study the specific legal and informational nature of the unsolved crime in comparison with the phenomenon of delinquency, special study and analysis to improve the efficiency of law enforcement.Methods of research are abstract-logical, systematic, statistical, study of documents. The main results of research. Unsolved crime has specific legal, statistical and informational na-ture as the crime phenomenon, which is expressed in cumulative statistical population of unsolved crimes. An array of unsolved crimes is the sum of the number of acts, things of which is suspended and not terminated. The fault of the perpetrator in these cases is not proven, they are not considered by the court, it is not a conviction. Unsolved crime must be registered. Latent crime has a different informational nature. The main symptom of latent crimes is the uncertainty for the subjects of law enforcement, which delegated functions of identification, registration and accounting. Latent crime is not recorded. At the same time, there is a "border" area between the latent and unsolved crimes, which includes covered from the account of the crime. In modern Russia the majority of crimes covered from accounting by passing the decision about refusal in excitation of criminal case. Unsolved crime on their criminogenic consequences represents a significant danger to the public is higher compared to latent crime.It is conducted in the article a special analysis of the differences and similarities in the unsolved latent crime for the first time in criminological literature.The analysis proves the need for radical changes in the current Russian assessment of the state of crime and law enforcement to solve crimes. The article argues that an unsolved crime is a separate and, in contrast to latent crime, poorly understood phenomenon. However unsolved latent crime and have common features and areas of interaction.

  19. Original Research Hepatitis B virus seroprevalence among ...

    African Journals Online (AJOL)

    genetic markers, and liver biopsy, amongst others.9,10 In. Malawi, screening for hepatitis B virus surface antigen. (HBsAg) in public hospitals .... produced in response to the core HBV antigen and persist for life, suggesting a past horizontal transmission in childhood and adulthood.21 Detection of HBV DNA could be useful.

  20. The Epstein-Barr virus DNA load in the peripheral blood of transplant recipients does not accurately reflect the burden of infected cells.

    Science.gov (United States)

    Fink, Susanne; Tsai, Ming-Han; Schnitzler, Paul; Zeier, Martin; Dreger, Peter; Wuchter, Patrick; Bulut, Olcay C; Behrends, Uta; Delecluse, Henri-Jacques

    2017-01-01

    Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV) load in the peripheral blood. Here, we quantitated the EBV-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. These data indicated that there is no strong correlation between the number of infected cells and the EBV load (EBVL). This can be explained by a highly variable number of EBV copies per infected cell and by lytic replication in some cells. The plasma of these patients did not contain any free infectious viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that probably originates from cell debris and contributed to the total EBVL. Some of the investigated samples carried a highly variable number of infected cells in active latency, characterized by an expression of the Epstein-Barr nuclear antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2 nor lytic proteins. Patients with an increased EBVL represent a heterogeneous group of patients whose infection cannot be characterized by this method alone. Precise characterization of the origin of an increased EBVL, in particular, in terms of the number of EBV-infected cells, requires additional investigations including the number of EBV-encoded small RNA-positive cells. © 2016 Steunstichting ESOT.

  1. The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice.

    Science.gov (United States)

    Field, H J; Wildy, P

    1978-10-01

    The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.

  2. Polymicrobial infection and bacterium-mediated epigenetic modification of DNA tumor viruses contribute to pathogenesis.

    Science.gov (United States)

    Doolittle, J M; Webster-Cyriaque, J

    2014-04-29

    ABSTRACT The human body plays host to a wide variety of microbes, commensal and pathogenic. In addition to interacting with their host, different microbes, such as bacteria and viruses, interact with each other, sometimes in ways that exacerbate disease. In particular, gene expression of a number of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), is known to be regulated by epigenetic modifications induced by bacteria. These viruses establish latent infection in their host cells and can be reactivated by bacterial products. Viral reactivation has been suggested to contribute to periodontal disease and AIDS. In addition, bacterium-virus interactions may play a role in cancers, such as Kaposi's sarcoma, gastric cancer, and head and neck cancer. It is important to consider the effects of coexisting bacterial infections when studying viral diseases in vivo.

  3. Latent geometry of bipartite networks

    Science.gov (United States)

    Kitsak, Maksim; Papadopoulos, Fragkiskos; Krioukov, Dmitri

    2017-03-01

    Despite the abundance of bipartite networked systems, their organizing principles are less studied compared to unipartite networks. Bipartite networks are often analyzed after projecting them onto one of the two sets of nodes. As a result of the projection, nodes of the same set are linked together if they have at least one neighbor in common in the bipartite network. Even though these projections allow one to study bipartite networks using tools developed for unipartite networks, one-mode projections lead to significant loss of information and artificial inflation of the projected network with fully connected subgraphs. Here we pursue a different approach for analyzing bipartite systems that is based on the observation that such systems have a latent metric structure: network nodes are points in a latent metric space, while connections are more likely to form between nodes separated by shorter distances. This approach has been developed for unipartite networks, and relatively little is known about its applicability to bipartite systems. Here, we fully analyze a simple latent-geometric model of bipartite networks and show that this model explains the peculiar structural properties of many real bipartite systems, including the distributions of common neighbors and bipartite clustering. We also analyze the geometric information loss in one-mode projections in this model and propose an efficient method to infer the latent pairwise distances between nodes. Uncovering the latent geometry underlying real bipartite networks can find applications in diverse domains, ranging from constructing efficient recommender systems to understanding cell metabolism.

  4. Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

    Directory of Open Access Journals (Sweden)

    Júlia Souza Vidal

    2015-10-01

    Full Text Available AbstractLatent tuberculosis infection (LTBI and human immunodeficiency virus (HIV-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

  5. Hepatitis B Virus Genotype D Isolates Circulating in Chapeco, Southern Brazil, Originate from Italy.

    Directory of Open Access Journals (Sweden)

    Carolina Souza Gusatti

    Full Text Available Hepatitis B virus genotype A1 (HBV/A1, of African origin, is the most prevalent genotype in Brazil, while HBV/F predominates in the other South American countries. However, HBV/D is the most common in the three states of southern Brazil, where 'islands' of elevated prevalence, as Chapecó and other cities, have been described. In this study, 202 HBV chronic carriers attending in 2013 the viral hepatitis ambulatory of Chapecó, were investigated. In comparison with previous studies performed in the same ambulatory, a rapid aging of the HBV infected population was observed (mean age of the newly diagnosed patients increasing from 29.9 ± 10.3 years in 1996 to 44.4 ± 13.3 years in 2013, probably due to a singular vaccination schedule at Chapecó that included not only children but also adolescents. Phylogenetic and BLAST analyses (S region classified 91 HBV isolates into genotypes A (n = 3 and D (n = 88. The majority of HBV/D isolates were closely related to D3 sequences. To understand the reasons for the absence or near absence of genotypes A and F, and how HBV/D was introduced in the south of Brazil, HBV/D infected patients were inquired about their genealogical and geographical origins. Forty-three (52% patients have their four grandparents of Italian origin, vs. seven (8% who have their four grandparents of Brazilian origin. At all, 65 out of 83 (78% patients had at least one grandparent originating from Italy. Taking into consideration the fact that Italy is one of the few countries where subgenotype D3 is predominant, the results strongly suggested that HBV/D was introduced in Brazil through Italian immigration which culminated between 1870 and 1920.

  6. Primary varicella zoster virus infection in an Eritrean male refugee in Denmark

    DEFF Research Database (Denmark)

    Mathiasen, Victor Dahl; Wejse, Christian

    2017-01-01

    Primary infection with varicella zoster virus (VZV) in neonates, adults and in pregnancy may lead to severe disease and embryopathy. On the Northern hemisphere varicella is a mild childhood disease, but in tropical regions it typically occurs at later age and is more frequently observed among...... adolescents and adults. Disease presents with fever, malaise and a characteristic vesiculopapular rash (chickenpox) after an incubation period of 14 days on average. VZV is very contagious and transmission occurs mainly airborne. After infection, virus persists latent and prompts herpes zoster on reactivation...

  7. Experimental canine distemper infection as a means of demonstrating latent effects of subacute lead intoxication

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J.; McLeod, S.

    1976-01-01

    Observations on the response of the body to experimental infection with distemper virus in dogs previously dosed subacutely with lead have demonstrated a latent effect of lead on several body systems. Effects which indicated a relationship to earlier treatment with lead included evidence for stimulation of haemoglobin synthesis, changes to red blood cells resulting in increased destruction, increased vulnerability of the parenchymatous cells of the liver to damage, reduction in the weight of the skeleton and thyroid, an increase in weight of the thymus and brain and histopathological changes in the thymus. 21 references, 2 figures, 1 table.

  8. Zika: the origin and spread of a mosquito-borne virus

    Science.gov (United States)

    Kindhauser, Mary Kay; Allen, Tomas; Frank, Veronika; Santhana, Ravi Shankar

    2016-01-01

    Abstract Objective To describe the temporal and geographical distribution of Zika virus infection and associated neurological disorders, from 1947 to 1 February 2016, when Zika became a Public Health Emergency of International Concern (PHEIC). Methods We did a literature search using the terms “Zika” and “ZIKV” in PubMed, cross-checked the findings for completeness against other published reviews and added formal notifications to WHO submitted under the International Health Regulations. Findings From the discovery of Zika virus in Uganda in 1947 to the declaration of a PHEIC by the World Health Organization (WHO) on 1 February 2016, a total of 74 countries and territories had reported human Zika virus infections. The timeline in this paper charts the discovery of the virus (1947), its isolation from mosquitos (1948), the first human infection (1952), the initial spread of infection from Asia to a Pacific island (2007), the first known instance of sexual transmission (2008), reports of Guillain-Barré syndrome (2014) and microcephaly (2015) linked to Zika infections and the first appearance of Zika in the Americas (from 2015). Conclusion Zika virus infection in humans appears to have changed in character as its geographical range has expanded from equatorial Africa and Asia. The change is from an endemic, mosquito-borne infection causing mild illness to one that can cause large outbreaks linked with neurological sequelae and congenital abnormalities. PMID:27708473

  9. Proteomic Profiling of a Primary CD4+ T Cell Model of HIV-1 Latency Identifies Proteins Whose Differential Expression Correlates with Reactivation of Latent HIV-1.

    Science.gov (United States)

    Saha, Jamaluddin Md; Liu, Hongbing; Hu, Pei-Wen; Nikolai, Bryan C; Wu, Hulin; Miao, Hongyu; Rice, Andrew P

    2018-01-01

    The latent HIV-1 reservoir of memory CD4 + T cells that persists during combination antiviral therapy prevents a cure of infection. Insight into mechanisms of latency and viral reactivation are essential for the rational design of strategies to reduce the latent reservoir. In this study, we quantified the levels of >2,600 proteins in the CCL19 primary CD4 + T cell model of HIV-1 latency. We profiled proteins under conditions that promote latent infection and after cells were treated with phorbol 12-myristate 13-acetate (PMA) + ionomycin, which is known to efficiently induce reactivation of latent HIV-1. In an analysis of cells from two healthy blood donors, we identified 61 proteins that were upregulated ≥2-fold, and 36 proteins that were downregulated ≥2-fold under conditions in which latent viruses were reactivated. These differentially expressed proteins are, therefore, candidates for cellular factors that regulate latency or viral reactivation. Two unexpected findings were obtained from the proteomic data: (1) the interactions among the majority of upregulated proteins are largely undetermined in published protein-protein interaction networks and (2) downregulated proteins are strongly associated with Gene Ontology terms related to mitochondrial protein synthesis. This proteomic data set provides a useful resource for future mechanistic studies of HIV-1 latency.

  10. Data on the interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-09-01

    The data in this article supports the research paper entitled "Interexaminer variation of minutia markup on latent fingerprints" [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the "White Box Latent Print Examiner Study," in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent.

  11. Appearance of reassortant European avian-origin H1 influenza A viruses of swine in Vietnam.

    Science.gov (United States)

    Takemae, N; Nguyen, P T; Le, V T; Nguyen, T N; To, T L; Nguyen, T D; Pham, V P; Vo, H V; Le, Q V T; Do, H T; Nguyen, D T; Uchida, Y; Saito, T

    2018-03-06

    Three subtypes-H1N1, H1N2 and H3N2-of influenza A viruses of swine (IAVs-S) are currently endemic in swine worldwide, but there is considerable genotypic diversity among each subtype and limited geographical distribution. Through IAVs-S monitoring in Vietnam, two H1N2 influenza A viruses were isolated from healthy pigs in Ba Ria-Vung Tau Province, Southern Vietnam, on 2 December 2016. BLAST and phylogenetic analyses revealed that their HA and NA genes were derived from those of European avian-like H1N2 IAVs-S that contained avian-origin H1 and human-like N2 genes, and were particularly closely related to those of IAVs-S circulating in the Netherlands, Germany or Denmark. In addition, the internal genes of these Vietnamese isolates were derived from human A(H1N1)pdm09 viruses, suggesting that the Vietnamese H1N2 IAVs-S are reassortants between European H1N2 IAVs-S and human A(H1N1)pdm09v. The appearance of European avian-like H1N2 IAVs-S in Vietnam marks their first transmission outside Europe. Our results and statistical analyses of the number of live pigs imported into Vietnam suggest that the European avian-like H1N2 IAVs-S may have been introduced into Vietnam with their hosts through international trade. These findings highlight the importance of quarantining imported pigs to impede the introduction of new IAVs-S. © 2018 Blackwell Verlag GmbH.

  12. Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Sajal K. Ghosh

    2012-01-01

    Full Text Available Epstein-Barr virus (EBV is the causal agent in the etiology of Burkitt’s lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin’s and non-Hodgkin’s lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies.

  13. A flexible latent class approach to estimating test-score reliability

    NARCIS (Netherlands)

    van der Palm, D.W.; van der Ark, L.A.; Sijtsma, K.

    2014-01-01

    The latent class reliability coefficient (LCRC) is improved by using the divisive latent class model instead of the unrestricted latent class model. This results in the divisive latent class reliability coefficient (DLCRC), which unlike LCRC avoids making subjective decisions about the best solution

  14. On the explaining-away phenomenon in multivariate latent variable models.

    Science.gov (United States)

    van Rijn, Peter; Rijmen, Frank

    2015-02-01

    Many probabilistic models for psychological and educational measurements contain latent variables. Well-known examples are factor analysis, item response theory, and latent class model families. We discuss what is referred to as the 'explaining-away' phenomenon in the context of such latent variable models. This phenomenon can occur when multiple latent variables are related to the same observed variable, and can elicit seemingly counterintuitive conditional dependencies between latent variables given observed variables. We illustrate the implications of explaining away for a number of well-known latent variable models by using both theoretical and real data examples. © 2014 The British Psychological Society.

  15. Latent fingermark development using low-vacuum vaporization of ninhydrin.

    Science.gov (United States)

    Chen, Chun-Chieh; Yang, Chao-Kai; Liao, Jeh-Shane; Wang, Sheng-Meng

    2015-12-01

    The vacuum technique is a method of vaporizing a solid material to its gas phase, helping deposit reagents gently on target surfaces to develop latent fingermarks. However, this application is rarely reported in the literature. In this study, a homemade fume hood with a built-in vacuum control system and programmable heating system designed by the Taiwan Criminal Investigation Bureau is introduced. Factors that affect the instrument's performance in developing fingermarks are discussed, including the quantity of chemicals for vaporization, heating program arrangement, and paper of different materials. The results show that fingermarks are effectively developed by vaporizing solid ninhydrin. This would be an alternative application in selecting a solvent-free method for protecting the environment and reducing health hazards in the lab. In terms of the heating program, the result indicates that under a low-vacuum condition (50 mTorr), 80-90 °C is a suitable temperature range for ninhydrin vaporization, allowing ninhydrin to be vaporized without bumping and waste. In terms of the performance on different material papers, this instrument demonstrates its capacity by developing latent fingermarks on thermal paper without discoloration or damaging the original writing, and the same results are also observed on Taiwan and United States banknotes. However, a coherent result could be hardly obtained using the same vaporization setting because different banknotes have their own surface features and water absorption ability or other unique factors may influence the effect of ninhydrin deposition. This study provides a reliable application for developing latent fingermarks without using solvents, and it is also expected to contribute to environmental protection along with the trend of green chemistry technology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Recent advances in vaccine development for herpes simplex virus types I and II.

    Science.gov (United States)

    Coleman, Jeffrey L; Shukla, Deepak

    2013-04-01

    Despite recent advances in vaccine design and strategies, latent infection with herpes simplex virus (HSV) remains a formidable challenge. Approaches involving live-attenuated viruses and inactivated viral preparations were popular throughout the twentieth century. In the past ten years, many vaccine types, both prophylactic or therapeutic, have contained a replication-defective HSV, viral DNA or glycoproteins. New research focused on the mechanism of immune evasion by the virus has involved developing vaccines with various gene deletions and manipulations combined with the use of new and more specific adjuvants. In addition, new "prime-boost" methods of strengthening the vaccine efficacy have proven effective, but there have also been flaws with some recent strategies that appear to have compromised vaccine efficacy in humans. Given the complicated lifecycle of HSV and its unique way of spreading from cell-to-cell, it can be concluded that the development of an ideal vaccine needs new focus on cell-mediated immunity, better understanding of the latent viral genome and serious consideration of gender-based differences in immunity development among humans. This review summarizes recent developments made in the field and sheds light on some potentially new ways to conquer the problem including development of dual-action prophylactic microbicides that prohibit viral entry and, in addition, induce a strong antigen response.

  17. Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Katrin Hartmann

    2015-12-01

    Full Text Available Feline immunodeficiency virus (FIV is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.

  18. Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

    International Nuclear Information System (INIS)

    Rainio, Eeva-Marja; Ahlfors, Helena; Carter, Kara L.; Ruuska, Marja; Matikainen, Sampsa; Kieff, Elliott; Koskinen, Paeivi J.

    2005-01-01

    Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth

  19. Study of the titers of Anti-Epstein-Barr virus antibodies in the sera of atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Mitoshi; Kusunoki, Yoichiro; Kyoizumi, Seishi; Ozaki, Kyoko; Mizuno, Shoichi; Cologne, J.B.

    1993-12-31

    Antibody titers to Epstein-Barr virus antigens were determined in the sera of 372 atomic bomb survivors to evaluate the effect of the previous radiation exposure on immune competence against the latent infection of the virus. The proportion of persons with high titers ({>=} 1:40) of IgG antibodies to the early antigen was significantly elevated in the exposed survivors. Furthermore, the distribution of IgM titers against the viral capsid antigen was significantly affected by radiation dose with an increased occurrence of titers of 1:5 and 1:10 in the exposed persons, although the dose effect was only marginally suggestive when persons with rheumatoid factor were eliminated from the analysis. These results suggest that reactivation of Epstein-Barr virus in the latent stage occurs more frequently in the survivors, even though this might not be affected by the radiation dose. Otherwise, there was neither an increased trend in the prevalence of high titers ({>=} 1:640) of IgG antibodies to the viral capsid antigen among the exposed people nor a correlation between the radiation exposure and distributions of titers of IgA antibodies to the viral capsid antigen or antibodies to the anti-Epstein-Barr virus-associated nuclear antigen. (author).

  20. Study of the titers of Anti-Epstein-Barr virus antibodies in the sera of atomic bomb survivors

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Kusunoki, Yoichiro; Kyoizumi, Seishi; Ozaki, Kyoko; Mizuno, Shoichi; Cologne, J.B.

    1993-01-01

    Antibody titers to Epstein-Barr virus antigens were determined in the sera of 372 atomic bomb survivors to evaluate the effect of the previous radiation exposure on immune competence against the latent infection of the virus. The proportion of persons with high titers (≥ 1:40) of IgG antibodies to the early antigen was significantly elevated in the exposed survivors. Furthermore, the distribution of IgM titers against the viral capsid antigen was significantly affected by radiation dose with an increased occurrence of titers of 1:5 and 1:10 in the exposed persons, although the dose effect was only marginally suggestive when persons with rheumatoid factor were eliminated from the analysis. These results suggest that reactivation of Epstein-Barr virus in the latent stage occurs more frequently in the survivors, even though this might not be affected by the radiation dose. Otherwise, there was neither an increased trend in the prevalence of high titers (≥ 1:640) of IgG antibodies to the viral capsid antigen among the exposed people nor a correlation between the radiation exposure and distributions of titers of IgA antibodies to the viral capsid antigen or antibodies to the anti-Epstein-Barr virus-associated nuclear antigen. (author)

  1. EVIDENCE OF EPSTEIN-BARR VIRUS ASSOCIATION WITH HEAD AND NECK CANCERS: A REVIEW.

    Science.gov (United States)

    Prabhu, Soorebettu R; Wilson, David F

    2016-01-01

    Epstein-Barr virus (EBV) is ubiquitous: over 90% of the adult population is infected with this virus. EBV is capable of infecting both B lymphocytes and epithelial cells throughout the body including the head and neck region. Transmission occurs mainly by exchange of saliva. The infection is asymptomatic or mild in children but, in adolescents and young adults, it causes infectious mononucleosis, a self-limiting disease characterized by lethargy, sore throat, fever and lymphadenopathy. Once established, the virus often remains latent and people become lifelong carriers without experiencing disease. However, in some people, the latent virus is capable of causing malignant tumours, such as nasopharyngeal carcinoma and various B- and T-cell lymphomas, at sites including the head, neck and oropharyngeal region. As lymphoma is the second-most common malignant disease of the head, neck and oral region after squamous cell carcinoma, oral health care workers including dentists and specialists have a responsibility to carry out a thorough clinical examination of this anatomical region with a view to identifying and diagnosing lesions that may represent lymphomas. Early detection allows early treatment resulting in better prognosis. The focus of this review is on the morphology, transmission and carcinogenic properties of EBV and clinical and diagnostic aspects of a range of EBV-associated malignancies occurring in the head, neck and oral region. As carcinogenic agents, viruses contribute to a significant proportion of the global cancer burden: approximately 15% of all human cancers, worldwide, are attributable to viruses.1,2 Serologic and epidemiologic studies are providing mounting evidence of an etiologic association between viruses and head and neck malignancies.3 To update oral and maxillofacial surgeons and oral medicine specialists and raise awareness of this association, we recently reviewed the evidence of the etiologic role of human papillomavirus in oral disease.4

  2. The 2012 dengue outbreak in Madeira: exploring the origins.

    Science.gov (United States)

    Wilder-Smith, A; Quam, M; Sessions, O; Rocklov, J; Liu-Helmersson, J; Franco, L; Khan, K

    2014-02-27

    In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

  3. Subclinical Shed of Infectious Varicella zoster Virus in Astronauts

    Science.gov (United States)

    Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.

    2007-01-01

    Aerosol borne varicella zoster virus (VZV) enters the nasopharynx and replicates in tonsillar T-cells, resulting in viremia and varicella (chickenpox). Virus then becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis (1). Decades later, as cell-mediated immunity to VZV declines (4), latent VZV can reactivate to produce zoster (shingles). Infectious VZV is present in patients with varicella or zoster, but shed of infectious virus in the absence of disease has not been shown. We previously detected VZV DNA in saliva of astronauts during and shortly after spaceflight, suggesting stress induced subclinical virus reactivation (3). We show here that VZV DNA as well as infectious virus in present in astronaut saliva. VZV DNA was detected in saliva during and after a 13-day spaceflight in 2 of 3 astronauts (Fig. panel A). Ten days before liftoff, there was a rise in serum anti-VZV antibody in subjects 1 and 2, consistent with virus reactivation. In subject 3, VZV DNA was not detected in saliva, and there was no rise in anti-VZV antibody titer. Subject 3 may have been protected from virus reactivation by having zoster DNA was detected in astronaut saliva months before spaceflight, or in saliva of 10 age/sex-matched healthy control subjects sampled on alternate days for 3 weeks (88 saliva samples). Saliva taken 2-6 days after landing from all 3 subjects was cultured on human fetal lung cells (Fig. panel B). Infectious VZV was recovered from saliva of subjects 1 and 2 on the second day after landing. Virus specificity was confirmed by antibody staining and DNA analysis which showed it to be VZV of European descent, common in the US (5). Further, both antibody staining and DNA PCR demonstrated that no HSV-1 was detected in any infected culture. This is the first report of infectious VZV shedding in the absence of clinical disease. Spaceflight presents a uniquely stressful environment which includes physical isolation and

  4. Extraction of latent images from printed media

    Science.gov (United States)

    Sergeyev, Vladislav; Fedoseev, Victor

    2015-12-01

    In this paper we propose an automatic technology for extraction of latent images from printed media such as documents, banknotes, financial securities, etc. This technology includes image processing by adaptively constructed Gabor filter bank for obtaining feature images, as well as subsequent stages of feature selection, grouping and multicomponent segmentation. The main advantage of the proposed technique is versatility: it allows to extract latent images made by different texture variations. Experimental results showing performance of the method over another known system for latent image extraction are given.

  5. Expression of Epstein-Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco-chewing population.

    Science.gov (United States)

    Reddy, Sujatha S; Sharma, Shivani; Mysorekar, Vijaya

    2017-07-01

    Oral cancer is the sixth most common malignancy in the world. Viruses are the causative agents of approximately 10-15% of all cancers worldwide (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral cancer are unclear. Literature search results are conflicting and dependent on various factors such as geographical/regional variations, sociocultural lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the first original observation about frequency of Epstein-Barr virus among South Indian tobacco-chewing patients to elucidate its involvement in oral carcinogenesis and to know whether this can be a valuable diagnostic and prognostic indicator. A total number of 75 tobacco chewer subjects aged between 23 and 76 years with histopathologically confirmed oral potentially malignant disorders (25), oral squamous cell carcinoma (25), and age-matched healthy controls (25) formed the study group. Immunohistochemical expression of Epstein-Barr virus latent membrane protein 1 was assessed among cases and healthy controls. Out of the total 75 subjects, six subjects (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative. The antigen positivity was observed among two cases of moderately differentiated oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls. No significant association between Epstein-Barr virus positivity was observed among oral potentially malignant disorders and oral squamous cell carcinoma among South Indian tobacco-chewing patients. This can be partially explained by the methodology employed, by the patient population analyzed and different habits in various geographical regions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton's tyrosine kinase and STAT3.

    Science.gov (United States)

    Incrocci, Ryan; Barse, Levi; Stone, Amanda; Vagvala, Sai; Montesano, Michael; Subramaniam, Vijay; Swanson-Mungerson, Michelle

    2017-01-01

    Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and -positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Additional studies indicate that the PI3K-regulated kinase, BTK, is responsible for phosphorylating STAT3, which ultimately mediates the LMP2A-dependent increase in IL-10. These data are the first to show that LMP2A signaling results in STAT3 phosphorylation in B cells through a PI3K/BTK-dependent pathway. With the use of BTK and STAT3 inhibitors to treat B cell lymphomas in clinical trials, these findings highlight the possibility of using new pharmaceutical approaches to treat EBV-associated lymphomas that express LMP2A. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Fitting Latent Cluster Models for Networks with latentnet

    Directory of Open Access Journals (Sweden)

    Pavel N. Krivitsky

    2007-12-01

    Full Text Available latentnet is a package to fit and evaluate statistical latent position and cluster models for networks. Hoff, Raftery, and Handcock (2002 suggested an approach to modeling networks based on positing the existence of an latent space of characteristics of the actors. Relationships form as a function of distances between these characteristics as well as functions of observed dyadic level covariates. In latentnet social distances are represented in a Euclidean space. It also includes a variant of the extension of the latent position model to allow for clustering of the positions developed in Handcock, Raftery, and Tantrum (2007.The package implements Bayesian inference for the models based on an Markov chain Monte Carlo algorithm. It can also compute maximum likelihood estimates for the latent position model and a two-stage maximum likelihood method for the latent position cluster model. For latent position cluster models, the package provides a Bayesian way of assessing how many groups there are, and thus whether or not there is any clustering (since if the preferred number of groups is 1, there is little evidence for clustering. It also estimates which cluster each actor belongs to. These estimates are probabilistic, and provide the probability of each actor belonging to each cluster. It computes four types of point estimates for the coefficients and positions: maximum likelihood estimate, posterior mean, posterior mode and the estimator which minimizes Kullback-Leibler divergence from the posterior. You can assess the goodness-of-fit of the model via posterior predictive checks. It has a function to simulate networks from a latent position or latent position cluster model.

  8. A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

    Science.gov (United States)

    Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

    2014-09-01

    Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    ORIGINAL ARTICLES. References. 1. UNAIDS. Report on the Global HTV/AIDS Epidemic. Geneva: June 2000. 2. Connor E..\\1, Sperling RS, Gelber R. et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovu dine treatment. N Eng! J Med 1994; 331:1173-1180. 3. Undegren ML ...

  10. Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie

    2014-01-01

    OBJECTIVE: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. METHODS: T cells were analyzed by flow cytometry and antibodies were...

  11. Heteroscedastic Latent Trait Models for Dichotomous Data.

    Science.gov (United States)

    Molenaar, Dylan

    2015-09-01

    Effort has been devoted to account for heteroscedasticity with respect to observed or latent moderator variables in item or test scores. For instance, in the multi-group generalized linear latent trait model, it could be tested whether the observed (polychoric) covariance matrix differs across the levels of an observed moderator variable. In the case that heteroscedasticity arises across the latent trait itself, existing models commonly distinguish between heteroscedastic residuals and a skewed trait distribution. These models have valuable applications in intelligence, personality and psychopathology research. However, existing approaches are only limited to continuous and polytomous data, while dichotomous data are common in intelligence and psychopathology research. Therefore, in present paper, a heteroscedastic latent trait model is presented for dichotomous data. The model is studied in a simulation study, and applied to data pertaining alcohol use and cognitive ability.

  12. Cryotherapy by encapsulation-dehydration is effective for in vitro eradication of latent viruses from ‘Marubakaido’ apple rootstock

    Science.gov (United States)

    Apple stem pitting virus (ASPV), Apple chlorotic leaf spot virus (ACLSV) and Apple stem grooving virus (ASGV) are several major viral pathogens of apple trees, responsible for substantial damage to the world's apple industry. This study aimed to evaluate the effectiveness of encapsulation-dehydratio...

  13. Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs

    Directory of Open Access Journals (Sweden)

    Viuff Birgitte M

    2011-09-01

    Full Text Available Abstract Background Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3 and swine/human (SA-alpha-2,6 influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA I, and II, and Sambucus Nigra (SNA. Furthermore, the predilection sites of swine influenza virus (SIV subtypes H1N1 and H1N2 as well as avian influenza virus (AIV subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. Results SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0% at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. Conclusions A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated

  14. Epstein Barr virus Latent Membrane Protein-1 enhances dendritic cell therapy lymph node migration, activation, and IL-12 secretion.

    Directory of Open Access Journals (Sweden)

    James M Termini

    Full Text Available Dendritic cells (DC are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1 of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5 expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines.

  15. Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Shannon-Lowe, Claire; Rickinson, Alan B; Bell, Andrew I

    2017-10-19

    Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  16. 134 original article prevalence of rubella virus-specific ...

    African Journals Online (AJOL)

    boaz

    ABSTRACT. Background: Rubella is a self-limiting disease that causes congenital rubella syndrome (CRS) when rubella virus (RV) infects women in the first trimester of pregnancy. Objective: To assess a population of pregnant women attending antenatal clinics in two tertiary hospitals in southwestern. Nigeria for anti-RV ...

  17. UV radiation and mouse models of herpes simplex virus infection

    International Nuclear Information System (INIS)

    Norval, Mary; El-Ghorr, A.A.

    1996-01-01

    Orolabial human infections with herpes simplex virus type 1 (HSV-1) are very common; following the primary epidermal infection, the virus is retained in a latent form in the trigeminal ganglia from where it can reactivate and cause a recrudescent lesion. Recrudescences are triggered by various stimuli including exposure to sunlight. In this review three categories of mouse models are used to examine the effects of UV irradiation on HSV infections: these are UV exposure prior to primary infection, UV exposure as a triggering event for recrudescence and UV exposure prior to challenge with virus is mice already immunized to HSV. In each of these models immunosuppression occurs, which is manifest, in some instances, in increased morbidity or an increased rate of recrudescence. Where known, the immunological mechanisms involved in the models are summarized and their relevance to human infections considered. (Author)

  18. Latent lifestyle preferences and household location decisions

    Science.gov (United States)

    Walker, Joan L.; Li, Jieping

    2007-04-01

    Lifestyle, indicating preferences towards a particular way of living, is a key driver of the decision of where to live. We employ latent class choice models to represent this behavior, where the latent classes are the lifestyles and the choice model is the choice of residential location. Thus, we simultaneously estimate lifestyle groups and how lifestyle impacts location decisions. Empirical results indicate three latent lifestyle segments: suburban dwellers, urban dwellers, and transit-riders. The suggested lifestyle segments have intriguing policy implications. Lifecycle characteristics are used to predict lifestyle preferences, although there remain significant aspects that cannot be explained by observable variables.

  19. Tropical Gravity Wave Momentum Fluxes and Latent Heating Distributions

    Science.gov (United States)

    Geller, Marvin A.; Zhou, Tiehan; Love, Peter T.

    2015-01-01

    Recent satellite determinations of global distributions of absolute gravity wave (GW) momentum fluxes in the lower stratosphere show maxima over the summer subtropical continents and little evidence of GW momentum fluxes associated with the intertropical convergence zone (ITCZ). This seems to be at odds with parameterizations forGWmomentum fluxes, where the source is a function of latent heating rates, which are largest in the region of the ITCZ in terms of monthly averages. The authors have examined global distributions of atmospheric latent heating, cloud-top-pressure altitudes, and lower-stratosphere absolute GW momentum fluxes and have found that monthly averages of the lower-stratosphere GW momentum fluxes more closely resemble the monthly mean cloud-top altitudes rather than the monthly mean rates of latent heating. These regions of highest cloud-top altitudes occur when rates of latent heating are largest on the time scale of cloud growth. This, plus previously published studies, suggests that convective sources for stratospheric GW momentum fluxes, being a function of the rate of latent heating, will require either a climate model to correctly model this rate of latent heating or some ad hoc adjustments to account for shortcomings in a climate model's land-sea differences in convective latent heating.

  20. Learning Latent Vector Spaces for Product Search

    NARCIS (Netherlands)

    Van Gysel, C.; de Rijke, M.; Kanoulas, E.

    2016-01-01

    We introduce a novel latent vector space model that jointly learns the latent representations of words, e-commerce products and a mapping between the two without the need for explicit annotations. The power of the model lies in its ability to directly model the discriminative relation between

  1. How long ago did smallpox virus emerge?

    Science.gov (United States)

    Shchelkunov, Sergei N

    2009-01-01

    Unlike vertebrates, for which paleontological data are available, and RNA viruses, which display a high rate of genetic variation, an objective estimate of time parameters for the molecular evolution of DNA viruses, which display a low rate of accumulation of mutations, is a complex problem. Genomic studies of a set of smallpox (variola) virus (VARV) isolates demonstrated the patterns of phylogenetic relationships between geographic variants of this virus. Using archival data on smallpox outbreaks and the results of phylogenetic analyses of poxvirus genomes, different research teams have obtained contradictory data on the possible time point of VARV origin. I discuss the approaches used for dating of VARV evolution and adduce the arguments favoring its historically recent origin.

  2. Emerging viruses in the Felidae: shifting paradigms.

    Science.gov (United States)

    O'Brien, Stephen J; Troyer, Jennifer L; Brown, Meredith A; Johnson, Warren E; Antunes, Agostinho; Roelke, Melody E; Pecon-Slattery, Jill

    2012-02-01

    The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

  3. Relationship of intratumoural protein expression patterns to age and Epstein-Barr virus status in classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Ludvigsen, Maja; Kamper, Peter; Hamilton-Dutoit, Stephen Jacques

    2015-01-01

    In Western countries, the age distribution of Hodgkin lymphoma (HL) follows a characteristic bimodal curve showing an early and a late peak at approximately 35 and 70 yr, respectively. Furthermore, the presence of latent Epstein-Barr virus (EBV) genome in the Hodgkin Reed-Sternberg cells...

  4. Zika virus infection in Vietnam: current epidemic, strain origin, spreading risk, and perspective.

    Science.gov (United States)

    Chu, Dinh-Toi; Ngoc, Vo Truong Nhu; Tao, Yang

    2017-11-01

    Zika virus infection and its associated microcephaly have being receiving global concern. This infection has spread widely since the first outbreak was recorded in Africa in 1952. Now, it has been reported in over 70 countries on five continents including Africa, North and South America, Asia, and Europe. Vietnam is one of the most recent countries which had cases of Zika virus infection at the end of 2016. This country has also reported the first case of a microcephaly-born baby which was probably linked to Zika virus infection. However, information on the Zika virus epidemic in Vietnam is still limited. This brief report intends to update the current Zika virus epidemic, and to discuss challenges and perspectives in controlling this infection in Vietnam.

  5. Characterization of Cucumber Mosaic Virus Originating from Cucurbits in Serbia

    Directory of Open Access Journals (Sweden)

    Ana Vučurović

    2011-01-01

    Full Text Available Cucumber mosaic virus (CMV is considered one of the most economically importantplant viruses and has a worldwide distribution and a very wide host range including plantsfrom family Cucurbitaceae. In Serbia, on cucurbits CMV was detected in single and mixedinfections with Zucchini yellow mosaic virus (ZYMV and Watermelon mosaic virus (WMV. Viruses,including CMV, are constantly present in cucurbit crops, but their frequency changesby year and locality. Surveys and sample collections were conducted in cucurbit crops inthe period from 2008 to 2009 at 15 localities in Vojvodina province, and sample testing wascarried out using the DAS-ELISA method and commercially available antisera for six economicallymost important cucurbit viruses. In 2008, a total of 51 samples were collected from13 cucurbit crops of oilseed pumpkin Olinka variety, squash, and bottle gourd and CMV wasdetected in a total of 55% of tested samples with symptoms of viral infection. The most commoninfectious type was mixed infection with ZYMV and WMV (35.3%, and then mixedinfection with ZYMV (17.7% and WMV (2%. A total of 599 symptomatic samples of oilseedpumpkin Olinka variety, zucchini squash varieties Beogradska and Tosca, squash, and wintersquash were collected in 15 cucurbits crops in 2009. CMV was present in 4.4% of totalcollected samples, in single infections in 1.3%, and in mixed with WMV or ZYMV in 1.3%, and1.8%. Five CMV isolates were obtained by mechanical inoculations of N. glutinosa and oneof them was selected for further biological characterization. Test plants which were describedto be hosts of CMV expressed symptoms characteristic for those caused by CMV afterinoculations by isolate 115-08. CMV specific primers Au1u/Au2d were used to amplify an850 bp fragment using RT-PCR method. Amplified fragment encodes the entire viral coatprotein (CP gene and partial 5’ and 3’ UTRs of two selected CMV isolates. Amplified fragmentswere sequenced and deposited in the NCBI, where

  6. Cytokine profile in patients with early latent syphilis

    Directory of Open Access Journals (Sweden)

    Zakharov S.V.

    2018-03-01

    Full Text Available The purpose of this study was to study the change in the content of the most active cytokines (interleukins 6 and 10 during the formation of the immune response in patients with latent early syphilis, as well as to study the possible relationship between the concentrations of these cytokines and the duration of the disease. In 50 patients with early latent syphilis, the concentration of interleukins 6 and 10 in serum was studied. The serum level of interleukins was studied by the enzyme immunoassay. A statistically significant increase in the concentration of interleukin 6 in the blood of patients with latent syphilis and decrease in the interleukin 10 concentration in comparison with healthy people was established. At the same time, in patients with latent syphilis with term of infection for more than 1 year, interleukin 10 has been expressed, as compared with healthy people and, especially, with patients with syphilis with a duration of infection of up to 1 year. Along with this, a lower degree of increase in the concentration of interleukin 6 in patients with latent syphilis with a duration of infection over 1 year has been established, as compared with patients with latent syphilis with a term of infection up to 1 year, against the background of its increased concentration as compared with a group of healthy individuals.

  7. Partial characterization of Maize rayado fino virus isolates from Ecuador: phylogenetic analysis supports a Central American origin of the virus.

    Science.gov (United States)

    Chicas, Mauricio; Caviedes, Mario; Hammond, Rosemarie; Madriz, Kenneth; Albertazzi, Federico; Villalobos, Heydi; Ramírez, Pilar

    2007-06-01

    Maize rayado fino virus (MRFV) infects maize and appears to be restricted to, yet widespread in, the Americas. MRFV was previously unreported from Ecuador. Maize plants exhibiting symptoms of MRFV infection were collected at the Santa Catalina experiment station in Quito, Ecuador. RT-PCR reactions were performed on total RNA extracted from the symptomatic leaves using primers specific for the capsid protein (CP) gene and 3' non-translated region of MRFV and first strand cDNA as a template. Nucleotide sequence comparisons to previously sequenced MRFV isolates from other geographic regions revealed 88-91% sequence identity. Phylogenetic trees constructed using Maximum Likelihood, UPGMA, Minimal Evolution, Neighbor Joining, and Maximum Parsimony methods separated the MRFV isolates into four groups. These groups may represent geographic isolation generated by the mountainous chains of the American continent. Analysis of the sequences and the genetic distances among the different isolates suggests that MRFV may have originated in Mexico and/or Guatemala and from there it dispersed to the rest of the Americas.

  8. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Leslie L [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  9. Rapid and sensitive detection of novel avian-origin influenza A (H7N9 virus by reverse transcription loop-mediated isothermal amplification combined with a lateral-flow device.

    Directory of Open Access Journals (Sweden)

    Yiyue Ge

    Full Text Available A severe disease in humans caused by a novel avian-origin influenza A (H7N9 virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA and neuraminidase (NA genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9 virus infection.

  10. [sup 31]P-magnetic resonance spectroscopy: Impaired energy metabolism in latent hyperthyroidism. [sup 31]Phosphor-Kernspinspektroskopie: Gestoerter Energiestoffwechsel bei latenter Hyperthyreose

    Energy Technology Data Exchange (ETDEWEB)

    Theissen, P. (Klinik und Poliklinik fuer Nuklearmedizin, Univ. Koeln (Germany)); Kaldewey, S. (Klinik und Poliklinik fuer Nuklearmedizin, Univ. Koeln (Germany)); Moka, D. (Klinik und Poliklinik fuer Nuklearmedizin, Univ. Koeln (Germany)); Bunke, J. (Philips Medizin Systeme, Hamburg (Germany)); Voth, E. (Klinik und Poliklinik fuer Nuklearmedizin, Univ. Koeln (Germany)); Schicha, H. (Klinik und Poliklinik fuer Nuklearmedizin, Univ. Koeln (Germany))

    1993-06-01

    [sup 31]Phosphorous magnetic resonance spectroscopy allows an in vivo examination of energy metabolism. The present study was designed to evaluate whether in patients with latent hyperthyroidism alterations of muscle energy metabolism could be found similar to those observed in patients with overt hyperthyroidism. In 10 patients with overt hyperthyroidism before therapy and 20 with latent hyperthyroidism (also without therapy) and in 24 healthy volunteers magnetic resonance spectroscopy of the calf muscle was performed within a 1.5-Tesla magnet. Muscle concentrations of phosphocreatine, inorganic phosphate, and ATP were quantified compared to an external standard solution of K[sub 2]HPO[sub 4]. In the patients with overt hyperthyroidism and with latent hyperthyroidism a significant decrease of phosphocreatine was found. Further, the ATP concentration in patients with latent and manifest hyperthyroidism tended towards lower values. There were no significant differences in the decrease of phosphocreatine and ATP between both patient groups. Therefore, this study for the first time shows that alterations of energy metabolism in latent hyperthyroidism can be measured and that they are similar to those observed in overt hyperthyroidism. (orig.)

  11. Human immunodeficiency virus type 1 (HIV-1 reservoirs: mechanisms of latency and therapeutic strategies = Reservorios del virus de inmunodeficiencia humana tipo 1 (VIH-1: mecanismos de latencia y estrategias terapéuticas

    Directory of Open Access Journals (Sweden)

    Arcia Anaya, Eliuth David

    2014-07-01

    Full Text Available The human immunodeficiency virus type 1 can establish a latent infection in different kind of cells, which constitute the cellular reservoirs for the virus and allow its maintenance in the body indefinitely, even in patients with antiretroviral treatment. The main reservoirs of the HIV-1 are resting CD4+ T cells, although cells like monocytes/macrophages, dendritic cells, and other cells like hematopoietic stem cells and mast cells may be reservoirs of the virus. There are different mechanisms that contribute to the establishment and maintenance of latency in those cells, and include transcriptional interference, low availability of transcription factors, chromatin condensation, some microRNA that block viral translation, and so on. The knowledge of these mechanisms is crucial for the development of new drugs that may eliminate the virus from the body and lead to a cure.

  12. A developmental study of latent absolute pitch memory.

    Science.gov (United States)

    Jakubowski, Kelly; Müllensiefen, Daniel; Stewart, Lauren

    2017-03-01

    The ability to recall the absolute pitch level of familiar music (latent absolute pitch memory) is widespread in adults, in contrast to the rare ability to label single pitches without a reference tone (overt absolute pitch memory). The present research investigated the developmental profile of latent absolute pitch (AP) memory and explored individual differences related to this ability. In two experiments, 288 children from 4 to12 years of age performed significantly above chance at recognizing the absolute pitch level of familiar melodies. No age-related improvement or decline, nor effects of musical training, gender, or familiarity with the stimuli were found in regard to latent AP task performance. These findings suggest that latent AP memory is a stable ability that is developed from as early as age 4 and persists into adulthood.

  13. An Epstein-Barr virus anti-apoptotic protein constitutively expressed in transformed cells and implicated in burkitt lymphomagenesis: the Wp/BHRF1 link.

    Directory of Open Access Journals (Sweden)

    Gemma L Kelly

    2009-03-01

    Full Text Available Two factors contribute to Burkitt lymphoma (BL pathogenesis, a chromosomal translocation leading to c-myc oncogene deregulation and infection with Epstein-Barr virus (EBV. Although the virus has B cell growth-transforming ability, this may not relate to its role in BL since many of the transforming proteins are not expressed in the tumor. Mounting evidence supports an alternative role, whereby EBV counteracts the high apoptotic sensitivity inherent to the c-myc-driven growth program. In that regard, a subset of BLs carry virus mutants in a novel form of latent infection that provides unusually strong resistance to apoptosis. Uniquely, these virus mutants use Wp (a viral promoter normally activated early in B cell transformation and express a broader-than-usual range of latent antigens. Here, using an inducible system to express the candidate antigens, we show that this marked apoptosis resistance is mediated not by one of the extended range of EBNAs seen in Wp-restricted latency but by Wp-driven expression of the viral bcl2 homologue, BHRF1, a protein usually associated with the virus lytic cycle. Interestingly, this Wp/BHRF1 connection is not confined to Wp-restricted BLs but appears integral to normal B cell transformation by EBV. We find that the BHRF1 gene expression recently reported in newly infected B cells is temporally linked to Wp activation and the presence of W/BHRF1-spliced transcripts. Furthermore, just as Wp activity is never completely eclipsed in in vitro-transformed lines, low-level BHRF1 transcripts remain detectable in these cells long-term. Most importantly, recognition by BHRF1-specific T cells confirms that such lines continue to express the protein independently of any lytic cycle entry. This work therefore provides the first evidence that BHRF1, the EBV bcl2 homologue, is constitutively expressed as a latent protein in growth-transformed cells in vitro and, in the context of Wp-restricted BL, may contribute to virus

  14. Latent Transition Analysis with a Mixture Item Response Theory Measurement Model

    Science.gov (United States)

    Cho, Sun-Joo; Cohen, Allan S.; Kim, Seock-Ho; Bottge, Brian

    2010-01-01

    A latent transition analysis (LTA) model was described with a mixture Rasch model (MRM) as the measurement model. Unlike the LTA, which was developed with a latent class measurement model, the LTA-MRM permits within-class variability on the latent variable, making it more useful for measuring treatment effects within latent classes. A simulation…

  15. A Probability Distribution over Latent Causes, in the Orbitofrontal Cortex.

    Science.gov (United States)

    Chan, Stephanie C Y; Niv, Yael; Norman, Kenneth A

    2016-07-27

    The orbitofrontal cortex (OFC) has been implicated in both the representation of "state," in studies of reinforcement learning and decision making, and also in the representation of "schemas," in studies of episodic memory. Both of these cognitive constructs require a similar inference about the underlying situation or "latent cause" that generates our observations at any given time. The statistically optimal solution to this inference problem is to use Bayes' rule to compute a posterior probability distribution over latent causes. To test whether such a posterior probability distribution is represented in the OFC, we tasked human participants with inferring a probability distribution over four possible latent causes, based on their observations. Using fMRI pattern similarity analyses, we found that BOLD activity in the OFC is best explained as representing the (log-transformed) posterior distribution over latent causes. Furthermore, this pattern explained OFC activity better than other task-relevant alternatives, such as the most probable latent cause, the most recent observation, or the uncertainty over latent causes. Our world is governed by hidden (latent) causes that we cannot observe, but which generate the observations we see. A range of high-level cognitive processes require inference of a probability distribution (or "belief distribution") over the possible latent causes that might be generating our current observations. This is true for reinforcement learning and decision making (where the latent cause comprises the true "state" of the task), and for episodic memory (where memories are believed to be organized by the inferred situation or "schema"). Using fMRI, we show that this belief distribution over latent causes is encoded in patterns of brain activity in the orbitofrontal cortex, an area that has been separately implicated in the representations of both states and schemas. Copyright © 2016 the authors 0270-6474/16/367817-12$15.00/0.

  16. Determination of Roles of Microgravity and Ionizing Radiation on the Reactivation of Epstein-Barr Virus In Vitro

    Science.gov (United States)

    Mehta, Satish K; Renner, Ashlie; Stowe, Raymond; Bloom, David; Pierson, Duane

    2015-01-01

    Astronauts experience symptomatic and asymptomatic herpes virus reactivation during spaceflight. We have shown increases in reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella zoster virus (VZV) and shedding in body fluids (saliva and urine) in astronauts during space travel. Alterations in immunity, increased stress hormone levels, microgravity, increased radiation, and other conditions unique to spaceflight may promote reactivation of latent herpes viruses. Unique mechanico-physico forces associated with spaceflight can have profound effects on cellular function, especially immune cells. In space flight analog studies such as Antarctica, bed rest studies, and NASA's undersea habitat (Aquarius), reactivation of these viruses occurred, but to a lesser extent than spaceflight. Spaceflight analogs model some spaceflight factors, but none of the analogs recreates all factors experienced in space. Most notably, microgravity and radiation are not included in many analogs. Stress, processed through the HPA axis and SAM systems, induces viral reactivation. However, the respective roles of microgravity and increased space radiation levels or if any synergy exists are not known. Therefore, we studied the effect of modeled space radiation and/or microgravity, independent of the immune system on the changes in cellular gene expression that results in viral (EBV) reactivation. The effects of modeled microgravity and low shear on EBV replication and cellular and EBV gene expression were studied in human B-lymphocyte cell cultures. Latently infected B-lymphocytes were propagated in the rotating wall bioreactor and irradiated with the various dosages of gamma irradiation. At specific time intervals following exposure to modeled microgravity, the cells and supernatant were harvested and reactivation of EBV were assessed by measuring EBV and gene expression, DNA methylation, and infectious virus production.

  17. Learning Latent Structure in Complex Networks

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai

    such as the Modularity, it has recently been shown that latent structure in complex networks is learnable by Bayesian generative link distribution models (Airoldi et al., 2008, Hofman and Wiggins, 2008). In this paper we propose a new generative model that allows representation of latent community structure......Latent structure in complex networks, e.g., in the form of community structure, can help understand network dynamics, identify heterogeneities in network properties, and predict ‘missing’ links. While most community detection algorithms are based on optimizing heuristic clustering objectives...... as in the previous Bayesian approaches and in addition allows learning of node specific link properties similar to that in the modularity objective. We employ a new relaxation method for efficient inference in these generative models that allows us to learn the behavior of very large networks. We compare the link...

  18. Plasmid origin of replication of herpesvirus papio: DNA sequence and enhancer function.

    Science.gov (United States)

    Loeb, D D; Sung, N S; Pesano, R L; Sexton, C J; Hutchison, C; Pagano, J S

    1990-01-01

    Herpesvirus papio (HVP) is a lymphotropic virus of baboons which is related to Epstein-Barr virus (EBV) and produces latent infection. The nucleotide sequence of the 5,775-base-pair (bp) EcoRI K fragment of HVP, which has previously been shown to confer the ability to replicate autonomously, has been determined. Within this DNA fragment is a region which bears structural and sequence similarity to the ori-P region of EBV. The HVP ori-P region has a 10- by 26-bp tandem array which is related to the 20- by 30-bp tandem array from the EBV ori-P region. In HVP there is an intervening region of 764 bp followed by five partial copies of the 26-bp monomer. Both the EBV and HVP 3' regions have the potential to form dyad structures which, however, differ in arrangement. We also demonstrate that a transcriptional enhancer which requires transactivation by a virus-encoded factor is present in the HVP ori-P. Images PMID:2159548

  19. H7N9 influenza A virus in turkeys in Minnesota

    Science.gov (United States)

    Lebarbenchon, Camille; Pedersen, J.C.; Sreevatsan, Srinand; Ramey, Andy M.; Dugan, Vivien G.; Halpin, R.A.; Ferro, Paul A.; Lupiani, B.; Enomoto, Shinichiro; Poulson, Rebecca L.; Smeltzer, M.; Cardona, Carol J.; Tompkins, S.; Wentworth, D.E.; Stallknecht, D.E.; Brown, J.

    2015-01-01

    Introductions of H7 Influenza A virus (IAV) from wild birds into poultry have been documented worldwide, resulting in varying degrees of morbidity and mortality. H7 IAV infection in domestic poultry has served as a source of human infection and disease. We report the detection of H7N9 subtype IAV in Minnesota turkey farms during 2009 and 2011. The full-genome was sequenced from eight isolates as well as the hemagglutinin (HA) and neuraminidase (NA) gene segments of H7 and N9 virus subtypes for 108 isolates from North American wild birds between 1986 and 2012. Through maximum likelihood and coalescent phylogenetic analyses, we identified the recent H7 and N9 IAV ancestors of the turkey-origin H7N9 IAV, estimated the time and geographic origin of the ancestral viruses, and determined the relatedness between the 2009 and the 2011 turkey-origin H7N9 IAV. Analyses supported that the 2009 and the 2011 viruses were distantly related genetically, suggesting that the two outbreaks arose from independent introduction events from wild birds. Our findings further support that the 2011 MN turkey-origin H7N9 virus was closely related to H7N9 IAV isolated in poultry in Nebraska during the same year. Although the precise origin of the wild-bird donor of the turkey-origin H7N9 IAV could not be determined, our findings suggest that, for both the NA and HA gene segments, the MN turkey-origin H7N9 viruses were related to viruses circulating in wild birds between 2006 and 2011 in the Mississippi flyway.

  20. Astrovirology: Viruses at Large in the Universe.

    Science.gov (United States)

    Berliner, Aaron J; Mochizuki, Tomohiro; Stedman, Kenneth M

    2018-02-01

    Viruses are the most abundant biological entities on modern Earth. They are highly diverse both in structure and genomic sequence, play critical roles in evolution, strongly influence terran biogeochemistry, and are believed to have played important roles in the origin and evolution of life. However, there is yet very little focus on viruses in astrobiology. Viruses arguably have coexisted with cellular life-forms since the earliest stages of life, may have been directly involved therein, and have profoundly influenced cellular evolution. Viruses are the only entities on modern Earth to use either RNA or DNA in both single- and double-stranded forms for their genetic material and thus may provide a model for the putative RNA-protein world. With this review, we hope to inspire integration of virus research into astrobiology and also point out pressing unanswered questions in astrovirology, particularly regarding the detection of virus biosignatures and whether viruses could be spread extraterrestrially. We present basic virology principles, an inclusive definition of viruses, review current virology research pertinent to astrobiology, and propose ideas for future astrovirology research foci. Key Words: Astrobiology-Virology-Biosignatures-Origin of life-Roadmap. Astrobiology 18, 207-223.

  1. Emerging Viruses in the Felidae: Shifting Paradigms

    Directory of Open Access Journals (Sweden)

    Meredith A. Brown

    2012-02-01

    Full Text Available The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

  2. Evaluating the Latent Structure of the MMPI-2 F(p) Scale in a Forensic Sample: A Taxometric Analysis

    Science.gov (United States)

    Strong, David R.; Glassmire, David M.; Frederick, Richard I.; Greene, Roger L.

    2006-01-01

    P. A. Arbisi and Y. S. Ben-Porath (1995) originally proposed that the Infrequency Psychopathology scale, F(p), be used as the final step in an algorithm to determine the validity of a Minnesota Multiphasic Personality Inventory-2 (MMPI-2) protocol. The current study used taxometric procedures to determine the latent structure of F(p) among…

  3. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2015-07-01

    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  4. Morphometry of latent palmprints as a function of time.

    Science.gov (United States)

    Barros, Rodrigo M; Faria, Bruna E F; Kuckelhaus, Selma A S

    2013-12-01

    In many crimes, the elapsed time between production and collecting fingermark traces is crucial. and a method able to detect the aging of latent prints would represent an improvement in forensic procedures. Considering that as the latent print gets older, substantial changes in the relative proportion of individual components secreted by skin glands could affect the morphology of ridges, morphometry could be a potential tool to assess the aging of latent fingermarks. Then, considering the very limited research in the field, the present work aims to evaluate the morphometry of latent palmprint ridges, as a function of time, in order to identify an aging pattern. The latent marks were deposited by 20 donors on glass microscope slides considering pressure and contact angle, and then were maintained under controlled environmental conditions. The morphometric study was conducted on marks developed with magnetic powder in 7 different time intervals after deposition (0, 5, 10, 15, 20, 25 or 30 days); 60 ridges were evaluated for each developed mark. The results showed that: 1) the method for the replacement and mixing of skin secretions on the palm was appropriate to ensure reproducibility of latent prints, and 2) considering the studied group, there was a time-dependent reduction in the width of ridges and on the percentage of visible ridges over 30 days. Results suggest the possibility of using the morphometric method to determine an aging profile of latent palmprints on glass surface, aiming for forensic purposes. © 2013.

  5. Screening of Potential Inhibitor against Coat Protein of Apple Chlorotic Leaf Spot Virus.

    Science.gov (United States)

    Purohit, Rituraj; Kumar, Sachin; Hallan, Vipin

    2018-06-01

    In this study, we analyzed Coat protein (CP) of Apple chlorotic leaf spot virus (ACLSV), an important latent virus on Apple. Incidence of the virus is upto 60% in various apple cultivars, affecting yield losses of the order of 10-40% (depending upon the cultivar). CP plays an important role as the sole building block of the viral capsid. Homology approach was used to model 193 amino acid sequence of the coat protein. We used various servers such as ConSurf, TargetS, OSML, COACH, COFACTOR for the prediction of active site residues in coat protein. Virtual screening strategy was employed to search potential inhibitors for CP. Top twenty screened molecules considered for drugability, and toxicity analysis and one potential molecule was further analyzed by docking analysis. Here, we reported a potent molecule which could inhibit the formation of viron assembly by targeting the CP protein of virus.

  6. Molecular epidemiology of novel swine origin influenza virus (S-OIV from Gwalior, India, 2009

    Directory of Open Access Journals (Sweden)

    Shukla Jyoti

    2011-06-01

    Full Text Available Abstract Background The H1N1pandemic virus is a newly emergent human influenza A virus that is closely related to a number of currently circulating pig viruses in the 'classic North American' and 'Eurasian' swine influenza virus lineages and thus referred as S-OIV. Since the first reports of the virus in humans in April 2009, H1N1 virus has spread to 168 countries and overseas territories. India also witnessed severe H1N1 pandemic virus epidemic with considerable morbidity and mortality in different parts starting from May 2009. Findings The suspected swine flu outbreak from Gwalior India during October- December 2009 was confirmed through S-OIV HA gene specific RT-LAMP and real time RT-PCR. Positive samples through CDC real time and Lamp assay were further processed for isolation of the virus. Full HA gene sequencing of the H1N1 isolates of Gwalior, India revealed 99% homology with California and other circulating novel swine flu viruses. Three major changes were observed at nucleotide level, while two major amino acid shifts were observed at the position C9W and I30M corresponding to the ORF with prototype strain. The HA gene sequence phylogeny revealed the circulation of two genetically distinct lineages belonging to Clade VII and Clade I of S-OIV. Conclusions Our findings also supported the earlier report about circulation of mixed genogroups of S-OIV in India. Therefore continuous monitoring of the genetic makeup of this newly emergent virus is essential to understand its evolution within the country.

  7. Development of a Vaccine Incorporating Killed Virus of Canine Origin for the Prevention of Canine Parvovirus Infection

    Science.gov (United States)

    Povey, C.

    1982-01-01

    A parvovirus of canine origin, cultured in a feline kidney cell line, was inactivated with formalin. Three pilot serials were produced and three forms of finished vaccine (nonadjuvanted, single adjuvanted and double adjuvanted) were tested in vaccination and challenge trials. A comparison was also made with two inactivated feline panleukopenia virus vaccines, one of which has official approval for use in dogs. The inactivated canine vaccine in nonadjuvanted, adjuvanted or double adjuvanted form was immunogenic in 20 of 20 vaccinated dogs. The double adjuvanted vaccine is selected as the one of choice on the basis of best and most persistent seriological response. PMID:7039811

  8. AFV1, a novel virus infecting hyperthermophilic archaea of the genus acidianus

    International Nuclear Information System (INIS)

    Bettstetter, Marcus; Peng Xu; Garrett, Roger A.; Prangishvili, David

    2003-01-01

    We describe a novel virus, AFV1, of the hyperthermophilic archaeal genus Acidianus. Filamentous virions are covered with a lipid envelope and contain at least five different proteins with molecular masses in the range of 23-130 kDa and a 20.8-kb-long linear double-stranded DNA. The virus has been assigned to the family Lipothrixviridae on the basis of morphotypic characteristics. Host range is confined to several strains of Acidianus and the virus persists in its hosts in a stable carrier state. The latent period of virus infection is about 4 h. Viral DNA was sequenced and sequence similarities were found to the lipothrixvirus SIFV, the rudiviruses SIRV1 and SIRV2, as well as to conjugative plasmids and chromosomes of the genus Sulfolobus. Exceptionally for the linear genomes of archaeal viruses, many short direct repeats, with the sequence TTGTT or close variants thereof, are closely clustered over 300 bp at each end of the genome. They are reminiscent of the telomeric ends of linear eukaryal chromosomes

  9. Incorporating direct marketing activity into latent attrition models

    NARCIS (Netherlands)

    Schweidel, David A.; Knox, George

    2013-01-01

    When defection is unobserved, latent attrition models provide useful insights about customer behavior and accurate forecasts of customer value. Yet extant models ignore direct marketing efforts. Response models incorporate the effects of direct marketing, but because they ignore latent attrition,

  10. Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

    Directory of Open Access Journals (Sweden)

    Wong Emily HM

    2010-08-01

    Full Text Available Abstract Background The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. Results Relative Synonymous Codon Usage (RSCU values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA. The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus. Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes. Conclusions Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.

  11. Epstein-Barr virus infection and related hematological diseases.

    Science.gov (United States)

    Sawada, Akihisa

    2016-01-01

    Once the Epstein-Barr virus (EBV) has infected a person, it then latently infects B cells. This latent infection lasts a lifetime. However, EBV can infect T or NK cells (T/NK cells) in rare cases. Therefore, EBV causes various hematological diseases. Among these diseases, CAEBV is regarded as the most problematic because, although it is not particularly uncommon, the diagnostic tests for this disease are not covered by health insurance, a serious illness in the "non-active" periods is lacking, and the appropriate motivation for early initiation of treatment can easily be lost. However, the symptoms may suddenly change; and if the manifestations are resistant when such exacerbation occurs, CAEBC is potentially lethal. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure. Once the diagnosis has been made, earlier treatment initiation, safer bridging to allogeneic HSCT with multi-drug chemotherapy, and then, planned HSCT can be completed more safely and thereby achieve a better outcome.

  12. Molecular cloning of osteoma-inducing replication-competent murine leukemia viruses from the RFB osteoma virus stock

    DEFF Research Database (Denmark)

    Pedersen, Lene; Behnisch, Werner; Schmidt, Jörg

    1992-01-01

    We report the molecular cloning of two replication-competent osteoma-inducing murine leukemia viruses from the RFB osteoma virus stock (M. P. Finkel, C. A. Reilly, Jr., B. O. Biskis, and I. L. Greco, p. 353-366, in C. H. G. Price and F. G. M. Ross, ed., Bone--Certain Aspects of Neoplasia, 1973......). Like the original RFB osteoma virus stock, viruses derived from the molecular RFB clones induced multiple osteomas in mice of the CBA/Ca strain. The cloned RFB viruses were indistinguishable by restriction enzyme analysis and by nucleotide sequence analysis of their long-terminal-repeat regions...

  13. Latent fingerprints on different type of screen protective films

    Directory of Open Access Journals (Sweden)

    Yuttana Sudjaroen

    2016-07-01

    Full Text Available The purpose of this research was to study the quality of latent fingerprint on different types of screen protective films including screen protector, matte screen protector, anti-fingerprint clear screen protector and anti-fingerprint matte screen protector by using black powder method in developing latent fingerprints. The fingerprints were performed by 10 volunteers whose fingers (right index, right thumb, left index and left thumb were stubbing at different types of screen protective films and subsequently latent fingerprints were developed by brushing with black powder. Automated Fingerprint Identification System (AFIS counted the numbers of minutiae points from 320 latent fingerprints. Anti-fingerprint matte screen protective film produced the best quality of latent fingerprint with an average minutiae point 72.65, followed by matte screen protective film, clear screen protective film and anti-fingerprint clear screen protective film with an average minutiae point of 155.2, 135.0 and 72.65 respectively. The quality of latent fingerprints developed between a clear and a matte surface of screen protective films showed a significant difference (sig>0.05, whereas the coat and the non-coat with anti-fingerprint chemical revealed a non-significant difference (sig<0.05 in their number of minutiae points.

  14. Epstein-Barr virus nuclear antigen 1 (EBNA1) induced cytotoxicity in epithelial cells is associated with EBNA1 degradation and processing

    International Nuclear Information System (INIS)

    Jones, Richard J.; Smith, Laura J.; Dawson, Christopher W.; Haigh, Tracy; Blake, Neil W.; Young, Lawrence S.

    2003-01-01

    Epstein-Barr virus nuclear antigen 1 (EBNA1) has a central role in the maintenance and segregation of the Epstein-Barr virus (EBV) episome and by virtue of a glycine-alanine repeat domain is prevented from being endogenously processed for recognition by HLA class I restricted cytotoxic T lymphocytes (CTLs). We found that EBNA1 expression resulted in growth inhibition and a G2/M arrest in human squamous epithelial cell lines (SCC12F, SVK) but not epithelial cell lines of glandular origin (Hela, Ad/AH). The cytotoxicity of EBNA1 was associated with EBNA1 degradation and both these effects were blocked in SCC12F cells expressing either the anti-apoptotic bcl-2 protein or the EBV homolog of bcl-2, BHRF1. The endogenous degradation of EBNA1 in SVK epithelial cells was associated with specific CTL recognition, an effect not evident in EBNA1-expressing Hela cells. Consistent with the inability of SVK cells to tolerate EBNA1 expression, studies with a recombinant EBV demonstrated that SVK cells are unable to maintain stable virus infection, whereas Hela cells are able to efficiently establish latent EBV infection. These data have important implications for both the cellular requirements necessary to sustain a stable EBV infection and for the possible role of CTL responses in controlling EBV infection of epithelial cells

  15. Enigmatic origin of hepatitis B virus: An ancient travelling companion or a recent encounter?

    Science.gov (United States)

    Zehender, Gianguglielmo; Ebranati, Erika; Gabanelli, Elena; Sorrentino, Chiara; Lo Presti, Alessandra; Tanzi, Elisabetta; Ciccozzi, Massimo; Galli, Massimo

    2014-01-01

    Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes, particularly those concerning the origin and dispersion histories of genotypes A, D, E and F and their subgenotypes. The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain. It is hypothesised that HBV evolutionary rates are time dependent, and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations. PMID:24976700

  16. Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia.

    Directory of Open Access Journals (Sweden)

    Monique van Velzen

    2013-08-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection results in lifelong chronic infection of trigeminal ganglion (TG neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates.

  17. Interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-07-01

    Latent print examiners often differ in the number of minutiae they mark during analysis of a latent, and also during comparison of a latent with an exemplar. Differences in minutia counts understate interexaminer variability: examiners' markups may have similar minutia counts but differ greatly in which specific minutiae were marked. We assessed variability in minutia markup among 170 volunteer latent print examiners. Each provided detailed markup documenting their examinations of 22 latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. An average of 12 examiners marked each latent. The primary factors associated with minutia reproducibility were clarity, which regions of the prints examiners chose to mark, and agreement on value or comparison determinations. In clear areas (where the examiner was "certain of the location, presence, and absence of all minutiae"), median reproducibility was 82%; in unclear areas, median reproducibility was 46%. Differing interpretations regarding which regions should be marked (e.g., when there is ambiguity in the continuity of a print) contributed to variability in minutia markup: especially in unclear areas, marked minutiae were often far from the nearest minutia marked by a majority of examiners. Low reproducibility was also associated with differences in value or comparison determinations. Lack of standardization in minutia markup and unfamiliarity with test procedures presumably contribute to the variability we observed. We have identified factors accounting for interexaminer variability; implementing standards for detailed markup as part of documentation and focusing future training efforts on these factors may help to facilitate transparency and reduce subjectivity in the examination process. Published by Elsevier Ireland Ltd.

  18. Latent variables and route choice behavior

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo; Bekhor, Shlomo; Pronello, Cristina

    2012-01-01

    In the last decade, a broad array of disciplines has shown a general interest in enhancing discrete choice models by considering the incorporation of psychological factors affecting decision making. This paper provides insight into the comprehension of the determinants of route choice behavior...... and bound algorithm. A hybrid model consists of measurement equations, which relate latent variables to measurement indicators and utilities to choice indicators, and structural equations, which link travelers’ observable characteristics to latent variables and explanatory variables to utilities. Estimation...

  19. Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes

    Energy Technology Data Exchange (ETDEWEB)

    Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

    2011-12-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  20. Victimization and Human Immunodeficiency Virus-Related Risk Among Transgender Women in India: A Latent Profile Analysis.

    Science.gov (United States)

    Willie, Tiara C; Chakrapani, Venkatesan; White Hughto, Jaclyn M; Kershaw, Trace S

    2017-12-01

    Globally, transgender women (TGW) experience multiple forms of victimization such as violence and discrimination that can place them at risk for poor sexual health. To date, research overlooks the heterogeneity in experiences of victimization among TGW. Furthermore, few studies have examined the association between victimization and sexual risk among TGW in India, despite the high burden of HIV and victimization in this community. Latent profile analysis was performed to identify patterns of victimization in a convenience sample of 299 TGW recruited from nongovernmental organizations across four states in India. Analysis of covariance was performed to examine differences in sexual risk (i.e., alcohol use before sex; inconsistent condom use with a male regular partner, a male causal partner, and a male paying partner; and having multiple sexual partners) between latent profiles. Five distinct profiles of Indian TGW were identified based on the type and severity of victimization: (1) Low victimization, (2) High verbal police victimization, (3) High verbal and physical police victimization, (4) Moderate victimization, and (5) High victimization. While controlling for age, education, income, HIV status, and marital status, results revealed that TGW in the moderate victimization and high victimization profiles had higher sexual risk than TGW in the low victimization and high verbal police victimization profiles. In addition, TGW in high verbal and physical police victimization profile had higher sexual risk than TGW in low victimization profile. These findings underscore the importance of tailoring sexual risk reduction interventions to the specific needs of TGW based on patterns of victimization.

  1. Lymphocryptovirus phylogeny and the origins of Epstein-Barr virus

    DEFF Research Database (Denmark)

    Ehlers, Bernhard; Spiess, Katja; Leendertz, Fabian

    2010-01-01

    Specimens from wild and captive primates were collected and novel members of the genus Lymphocryptovirus (subfamily Gammaherpesvirinae) were searched for utilizing PCR for the DNA polymerase gene. Twenty-one novel viruses were detected. Together with previous findings, more than 50 distinct lymph...

  2. A quantitative analysis on latent heat of an aqueous binary mixture.

    Science.gov (United States)

    Han, Bumsoo; Choi, Jeung Hwan; Dantzig, Jonathan A; Bischof, John C

    2006-02-01

    The latent heat during phase change of water-NaCl binary mixture was measured using a differential scanning calorimeter, and the magnitude for two distinct phase change events, water/ice and eutectic phase change, were analyzed considering the phase change characteristics of a binary mixture. During the analysis, the latent heat associated with each event was calculated by normalizing the amount of each endothermic peak with only the amount of sample participating in each event estimated from the lever rule for the phase diagram. The resulting latent heat of each phase change measured is 303.7 +/- 2.5 J/g for water/ice phase change, and 233.0 +/- 1.6 J/g for eutectic phase change, respectively regardless of the initial concentration of mixture. Although the latent heats of water/ice phase change in water-NaCl mixtures are closely correlated, further study is warranted to investigate the reason for smaller latent heat of water/ice phase change than that in pure water (335 J/g). The analysis using the lever rule was extended to estimate the latent heat of dihydrate as 115 J/g with the measured eutectic and water/ice latent heat values. This new analysis based on the lever rule will be useful to estimate the latent heat of water-NaCl mixtures at various concentrations, and may become a framework for more general analysis of latent heat of various biological solutions.

  3. Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

    Science.gov (United States)

    Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

    2011-08-01

    Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases.

  4. poLCA: An R Package for Polytomous Variable Latent Class Analysis

    Directory of Open Access Journals (Sweden)

    Drew A. Linzer

    2011-08-01

    Full Text Available poLCA is a software package for the estimation of latent class and latent class regression models for polytomous outcome variables, implemented in the R statistical computing environment. Both models can be called using a single simple command line. The basic latent class model is a finite mixture model in which the component distributions are assumed to be multi-way cross-classification tables with all variables mutually independent. The latent class regression model further enables the researcher to estimate the effects of covariates on predicting latent class membership. poLCA uses expectation-maximization and Newton-Raphson algorithms to find maximum likelihood estimates of the model parameters.

  5. Ruxolitinib and Tofacitinib Are Potent and Selective Inhibitors of HIV-1 Replication and Virus Reactivation In Vitro

    Science.gov (United States)

    Gavegnano, Christina; Detorio, Mervi; Montero, Catherine; Bosque, Alberto; Planelles, Vicente

    2014-01-01

    The JAK-STAT pathway is activated in both macrophages and lymphocytes upon human immunodeficiency virus type 1 (HIV-1) infection and thus represents an attractive cellular target to achieve HIV suppression and reduced inflammation, which may impact virus sanctuaries. Ruxolitinib and tofacitinib are JAK1/2 inhibitors that are FDA approved for rheumatoid arthritis and myelofibrosis, respectively, but their therapeutic application for treatment of HIV infection was unexplored. Both drugs demonstrated submicromolar inhibition of infection with HIV-1, HIV-2, and a simian-human immunodeficiency virus, RT-SHIV, across primary human or rhesus macaque lymphocytes and macrophages, with no apparent significant cytotoxicity at 2 to 3 logs above the median effective antiviral concentration. Combination of tofacitinib and ruxolitinib increased the efficacy by 53- to 161-fold versus that observed for monotherapy, respectively, and each drug applied alone to primary human lymphocytes displayed similar efficacy against HIV-1 containing various polymerase substitutions. Both drugs inhibited virus replication in lymphocytes stimulated with phytohemagglutinin (PHA) plus interleukin-2 (IL-2), but not PHA alone, and inhibited reactivation of latent HIV-1 at low-micromolar concentrations across the J-Lat T cell latency model and in primary human central memory lymphocytes. Thus, targeted inhibition of JAK provided a selective, potent, and novel mechanism to inhibit HIV-1 replication in lymphocytes and macrophages, replication of drug-resistant HIV-1, and reactivation of latent HIV-1 and has the potential to reset the immunologic milieu in HIV-infected individuals. PMID:24419350

  6. Structural identifiability of cyclic graphical models of biological networks with latent variables.

    Science.gov (United States)

    Wang, Yulin; Lu, Na; Miao, Hongyu

    2016-06-13

    Graphical models have long been used to describe biological networks for a variety of important tasks such as the determination of key biological parameters, and the structure of graphical model ultimately determines whether such unknown parameters can be unambiguously obtained from experimental observations (i.e., the identifiability problem). Limited by resources or technical capacities, complex biological networks are usually partially observed in experiment, which thus introduces latent variables into the corresponding graphical models. A number of previous studies have tackled the parameter identifiability problem for graphical models such as linear structural equation models (SEMs) with or without latent variables. However, the limited resolution and efficiency of existing approaches necessarily calls for further development of novel structural identifiability analysis algorithms. An efficient structural identifiability analysis algorithm is developed in this study for a broad range of network structures. The proposed method adopts the Wright's path coefficient method to generate identifiability equations in forms of symbolic polynomials, and then converts these symbolic equations to binary matrices (called identifiability matrix). Several matrix operations are introduced for identifiability matrix reduction with system equivalency maintained. Based on the reduced identifiability matrices, the structural identifiability of each parameter is determined. A number of benchmark models are used to verify the validity of the proposed approach. Finally, the network module for influenza A virus replication is employed as a real example to illustrate the application of the proposed approach in practice. The proposed approach can deal with cyclic networks with latent variables. The key advantage is that it intentionally avoids symbolic computation and is thus highly efficient. Also, this method is capable of determining the identifiability of each single parameter and

  7. Prevalence and risk factors of latent Tuberculosis among ...

    African Journals Online (AJOL)

    Background: Latent Tuberculosis treatment is a key tuberculosis control intervention. Adolescents are a high risk group that is not routinely treated in low income countries. Knowledge of latent Tuberculosis (TB) burden among adolescents may influence policy. Objectives: We determined the prevalence and risk factors of ...

  8. Latent viral reactivation is associated with changes in plasma antimicrobial protein concentrations during long-duration spaceflight

    Science.gov (United States)

    Spielmann, G.; Laughlin, M. S.; Kunz, H.; Crucian, B. E.; Quiriarte, H. D.; Mehta, S. K.; Pierson, D. L.; Simpson, R. J.

    2018-05-01

    Long duration spaceflights are associated with profound dysregulation of the immune system and latent viral reactivations. However, little is known on the impact of long duration spaceflight on innate immunity which raises concerns on crewmembers' ability to fight infections during a mission. The aim of this study was to determine the effects of spaceflight on plasma antimicrobial proteins (AMPs) and how these changes impact latent herpesvirus reactivations. Plasma, saliva and urine samples were obtained from 23 crewmembers before, during and after a 6-month mission on the International Space Station (ISS). Plasma AMP concentrations were determined by ELISA, and saliva Epstein-Barr virus (EBV) and varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. There was a non-significant increase in plasma HNP1-3 and LL-37 during the early and middle stages of the missions, which was significantly associated with changes in viral DNA during and after spaceflight. Plasma HNP1-3 and Lysozyme increased at the late mission stages in astronauts who had exhibited EBV and VZV reactivations during the early flight stages. Following return to Earth and during recovery, HNP1-3 and lysozyme concentrations were associated with EBV and VZV viral DNA levels, reducing the magnitude of viral reactivation. Reductions in plasma LL-37 upon return were associated with greater CMV reactivation. This study shows that biomarkers of innate immunity appeared to be partially restored after 6-months in space and suggests that following adaptation to the space environment, plasma HNP1-3 and lysozyme facilitate the control of EBV and VZV reactivation rate and magnitude in space and upon return on earth. However, the landing-associated decline in plasma LL-37 may enhance the rate of CMV reactivation in astronauts following spaceflight, potentially compromising crewmember health after landing.

  9. Effects of temperature on virogenesis of bluetongue virus serotype 11 in Culicoides variipennis sonorensis.

    Science.gov (United States)

    Mullens, B A; Tabachnick, W J; Holbrook, F R; Thompson, L H

    1995-01-01

    Culicoides variipennis sonorensis females were fed bluetongue virus serotype 11 mixed in sheep blood and were held at constant temperatures of 32, 27, 21 and 15 degrees C. Virogenesis, as measured by enzyme-linked immunosorbent assay (ELISA), proceeded significantly faster at higher temperatures. Based on ELISA absorbance > or = 0.2, some flies first were categorized as infected after 1 day, 2 days and 4 days at 32, 27 and 21 degrees C, respectively. Peak levels of virus antigen were seen after 5-7, 7-13 and 18-22 days for flies held at 32, 27 and 21 degrees C, respectively. There was no significant virus replication in flies held at 15 degrees C for 22 days, but latent virus replicated and was detected easily (44% infection) 4-10 days after these flies were transferred to 27 degrees C. The implications for temperature effects on bluetongue epizootiology are discussed.

  10. Assessing Trust and Effectiveness in Virtual Teams: Latent Growth Curve and Latent Change Score Models

    Directory of Open Access Journals (Sweden)

    Michael D. Coovert

    2017-08-01

    Full Text Available Trust plays a central role in the effectiveness of work groups and teams. This is the case for both face-to-face and virtual teams. Yet little is known about the development of trust in virtual teams. We examined cognitive and affective trust and their relationship to team effectiveness as reflected through satisfaction with one’s team and task performance. Latent growth curve analysis reveals both trust types start at a significant level with individual differences in that initial level. Cognitive trust follows a linear growth pattern while affective trust is overall non-linear, but becomes linear once established. Latent change score models are utilized to examine change in trust and also its relationship with satisfaction with the team and team performance. In examining only change in trust and its relationship to satisfaction there appears to be a straightforward influence of trust on satisfaction and satisfaction on trust. However, when incorporated into a bivariate coupling latent change model the dynamics of the relationship are revealed. A similar pattern holds for trust and task performance; however, in the bivariate coupling change model a more parsimonious representation is preferred.

  11. Elimination of cancer stem cells and reactivation of latent HIV-1 via AMPK activation: Common mechanism of action linking inhibition of tumorigenesis and the potential eradication of HIV-1.

    Science.gov (United States)

    Finley, Jahahreeh

    2017-07-01

    Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure. CSCs, which are largely resistant to chemoradiation therapy, are a subpopulation of cancer cells that exhibit characteristics similar to embryonic stem cells (ESCs), including self-renewal, multi-lineage differentiation, and the ability to initiate tumorigenesis. Interestingly, intracellular mechanisms that sustain quiescence and promote self-renewal in adult stem cells (ASCs) and CSCs likely also function to maintain latency of HIV-1 in CD4 + memory T cells. Although antiretroviral therapy is highly effective in controlling HIV-1 replication, the persistence of latent but replication-competent proviruses necessitates the development of compounds that are capable of selectively reactivating the latent virus, a method known as the "shock and kill" approach. Homeostatic proliferation in central CD4 + memory T (T CM ) cells, a memory T cell subset that exhibits limited self-renewal and differentiation and is a primary reservoir for latent HIV-1, has been shown to reinforce and stabilize the latent reservoir in the absence of T cell activation and differentiation. HIV-1 has also been found to establish durable and long-lasting latency in a recently discovered subset of CD4 + T cells known as T memory stem (T SCM ) cells. T SCM cells, compared to T CM cells, exhibit stem cell properties that more closely match those of ESCs and ASCs, including self-renewal and differentiation into all memory T cell subsets. It is our hypothesis

  12. Immune Responses of Chickens Infected with Wild Bird-Origin H5N6 Avian Influenza Virus

    Directory of Open Access Journals (Sweden)

    Shimin Gao

    2017-06-01

    Full Text Available Since April 2014, new infections of H5N6 avian influenza virus (AIV in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283 in Pallas’s sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015, whereas a virus (i.e., SW8 isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6. However, the pathogenicity, transmissibility, and host immune-related response of chickens infected by those wild bird-origin H5N6 AIVs remain unknown. In response, we examined the viral distribution and mRNA expression profiles of immune-related genes in chickens infected with both viruses. Results showed that the H5N6 AIVs were highly pathogenic to chickens and caused not only systemic infection in multiple tissues, but also 100% mortality within 3–5 days post-infection. Additionally, ZH283 efficiently replicated in all tested tissues and transmitted among chickens more rapidly than SW8. Moreover, quantitative real-time polymerase chain reaction analysis showed that following infection with H5N6, AIVs immune-related genes remained active in a tissue-dependent manner, as well as that ZH283 induced mRNA expression profiles such as TLR3, TLR7, IL-6, TNF-α, IL-1β, IL-10, IL-8, and MHC-II to a greater extent than SW8 in the tested tissues of infected chickens. Altogether, our findings help to illuminate the pathogenesis and immunologic mechanisms of H5N6 AIVs in chickens.

  13. Latent semantic analysis.

    Science.gov (United States)

    Evangelopoulos, Nicholas E

    2013-11-01

    This article reviews latent semantic analysis (LSA), a theory of meaning as well as a method for extracting that meaning from passages of text, based on statistical computations over a collection of documents. LSA as a theory of meaning defines a latent semantic space where documents and individual words are represented as vectors. LSA as a computational technique uses linear algebra to extract dimensions that represent that space. This representation enables the computation of similarity among terms and documents, categorization of terms and documents, and summarization of large collections of documents using automated procedures that mimic the way humans perform similar cognitive tasks. We present some technical details, various illustrative examples, and discuss a number of applications from linguistics, psychology, cognitive science, education, information science, and analysis of textual data in general. WIREs Cogn Sci 2013, 4:683-692. doi: 10.1002/wcs.1254 CONFLICT OF INTEREST: The author has declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

  14. A coarse to fine minutiae-based latent palmprint matching.

    Science.gov (United States)

    Liu, Eryun; Jain, Anil K; Tian, Jie

    2013-10-01

    With the availability of live-scan palmprint technology, high resolution palmprint recognition has started to receive significant attention in forensics and law enforcement. In forensic applications, latent palmprints provide critical evidence as it is estimated that about 30 percent of the latents recovered at crime scenes are those of palms. Most of the available high-resolution palmprint matching algorithms essentially follow the minutiae-based fingerprint matching strategy. Considering the large number of minutiae (about 1,000 minutiae in a full palmprint compared to about 100 minutiae in a rolled fingerprint) and large area of foreground region in full palmprints, novel strategies need to be developed for efficient and robust latent palmprint matching. In this paper, a coarse to fine matching strategy based on minutiae clustering and minutiae match propagation is designed specifically for palmprint matching. To deal with the large number of minutiae, a local feature-based minutiae clustering algorithm is designed to cluster minutiae into several groups such that minutiae belonging to the same group have similar local characteristics. The coarse matching is then performed within each cluster to establish initial minutiae correspondences between two palmprints. Starting with each initial correspondence, a minutiae match propagation algorithm searches for mated minutiae in the full palmprint. The proposed palmprint matching algorithm has been evaluated on a latent-to-full palmprint database consisting of 446 latents and 12,489 background full prints. The matching results show a rank-1 identification accuracy of 79.4 percent, which is significantly higher than the 60.8 percent identification accuracy of a state-of-the-art latent palmprint matching algorithm on the same latent database. The average computation time of our algorithm for a single latent-to-full match is about 141 ms for genuine match and 50 ms for impostor match, on a Windows XP desktop system with 2

  15. 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.

  16. Association between latent toxoplasmosis and cognition in adults: a cross-sectional study.

    Science.gov (United States)

    Gale, S D; Brown, B L; Erickson, L D; Berrett, A; Hedges, D W

    2015-04-01

    Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

  17. A Non-Gaussian Spatial Generalized Linear Latent Variable Model

    KAUST Repository

    Irincheeva, Irina; Cantoni, Eva; Genton, Marc G.

    2012-01-01

    We consider a spatial generalized linear latent variable model with and without normality distributional assumption on the latent variables. When the latent variables are assumed to be multivariate normal, we apply a Laplace approximation. To relax the assumption of marginal normality in favor of a mixture of normals, we construct a multivariate density with Gaussian spatial dependence and given multivariate margins. We use the pairwise likelihood to estimate the corresponding spatial generalized linear latent variable model. The properties of the resulting estimators are explored by simulations. In the analysis of an air pollution data set the proposed methodology uncovers weather conditions to be a more important source of variability than air pollution in explaining all the causes of non-accidental mortality excluding accidents. © 2012 International Biometric Society.

  18. A Non-Gaussian Spatial Generalized Linear Latent Variable Model

    KAUST Repository

    Irincheeva, Irina

    2012-08-03

    We consider a spatial generalized linear latent variable model with and without normality distributional assumption on the latent variables. When the latent variables are assumed to be multivariate normal, we apply a Laplace approximation. To relax the assumption of marginal normality in favor of a mixture of normals, we construct a multivariate density with Gaussian spatial dependence and given multivariate margins. We use the pairwise likelihood to estimate the corresponding spatial generalized linear latent variable model. The properties of the resulting estimators are explored by simulations. In the analysis of an air pollution data set the proposed methodology uncovers weather conditions to be a more important source of variability than air pollution in explaining all the causes of non-accidental mortality excluding accidents. © 2012 International Biometric Society.

  19. Collective decisions among bacterial viruses

    Science.gov (United States)

    Joh, Richard; Mileyko, Yuriy; Voit, Eberhard; Weitz, Joshua

    2010-03-01

    For many temperate bacteriophages, the decision of whether to kill hosts or enter a latent state depends on the multiplicity of infection. In this talk, I present a quantitative model of gene regulatory dynamics to describe how phages make collective decisions within host cells. Unlike most previous studies, the copy number of viral genomes is treated as a variable. In the absence of feedback loops, viral mRNA transcription is expected to be proportional to the viral copy number. However, when there are nonlinear feedback loops in viral gene regulation, our model shows that gene expression patterns are sensitive to changes in viral copy number and there can be a domain of copy number where the system becomes bistable. Hence, the viral copy number is a key control parameter determining host cell fates. This suggests that bacterial viruses can respond adaptively to changes in population dynamics, and can make alternative decisions as a bet-hedging strategy. Finally, I present a stochastic version of viral gene regulation and discuss speed-accuracy trade-offs in the context of cell fate determination by viruses.

  20. Caffeine/nutrition interaction in the rat brain: Influence on latent inhibition and cortical spreading depression.

    Science.gov (United States)

    de Aguiar, Márlison José Lima; de Aguiar, Cilene Rejane Ramos Alves; Guedes, Rubem Carlos Araújo

    2011-01-10

    Caffeine, like malnutrition, can produce behavioral and electrophysiological alterations. However, the interaction of both factors remains unclear. Here this interaction has been studied in male Wistar rats previously malnourished during the lactation period by feeding their dams the "regional basic diet" of Northeast Brazil, containing about 8% protein, predominantly from vegetable sources (RBD(8)). At 70-75days of life, a subset of the pups was treated intraperitoneally with 30mg/kg caffeine for 4days while being tested according to the behavioral model of latent inhibition. Another group was subjected to an electrophysiological recording of the phenomenon known as cortical spreading depression, and the effects of caffeine injected during the recording session were evaluated. Caffeine did not affect cortical spreading depression, but antagonized latent inhibition in both the RBD(8)-malnourished rats and in the well-nourished control group fed a chow diet with 22% protein. This effect of caffeine was not seen in malnourished rats fed a protein-supplemented RBD (protein increased to 22% by increasing the proportion of foodstuffs from vegetable origin; RBD(22) group), suggesting that the amino acid imbalance of this diet may modulate the caffeine effects on latent inhibition. The results indicate a differential effect of caffeine in the latent inhibition behavioral model, as compared to the cortical spreading depression phenomenon, and this effect is influenced by the early nutritional status of the animal. We suggest that caffeine may modulate dopaminergic subcortical receptors participating in attention processes, but does not interact at the cortical level, in a way that would affect cortical spreading depression. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Viruses and the nucleolus: the fatal attraction.

    Science.gov (United States)

    Salvetti, Anna; Greco, Anna

    2014-06-01

    Viruses are small obligatory parasites and as a consequence, they have developed sophisticated strategies to exploit the host cell's functions to create an environment that favors their own replication. A common feature of most - if not all - families of human and non-human viruses concerns their interaction with the nucleolus. The nucleolus is a multifunctional nuclear domain, which, in addition to its well-known role in ribosome biogenesis, plays several crucial other functions. Viral infection induces important nucleolar alterations. Indeed, during viral infection numerous viral components localize in nucleoli, while various host nucleolar proteins are redistributed in other cell compartments or are modified, and non-nucleolar cellular proteins reach the nucleolus. This review highlights the interactions reported between the nucleolus and some human or animal viral families able to establish a latent or productive infection, selected on the basis of their known interactions with the nucleolus and the nucleolar activities, and their links with virus replication and/or pathogenesis. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Latent-failure risk estimates for computer control

    Science.gov (United States)

    Dunn, William R.; Folsom, Rolfe A.; Green, Owen R.

    1991-01-01

    It is shown that critical computer controls employing unmonitored safety circuits are unsafe. Analysis supporting this result leads to two additional, important conclusions: (1) annual maintenance checks of safety circuit function do not, as widely believed, eliminate latent failure risk; (2) safety risk remains even if multiple, series-connected protection circuits are employed. Finally, it is shown analytically that latent failure risk is eliminated when continuous monitoring is employed.

  3. Exposing Latent Information in Folksonomies for Reasoning

    Science.gov (United States)

    2010-01-14

    1.73 $.") http://www.w3.org/2006/07/SWD/ SKOS /reference/20081001/ Spiteri, L.F. (2007) "The structure and form of folksonomy tags: The road to the...Exposing Latent Information in Folksonomies for Reasoning January 14, 2010 Sponsored by Defense Advanced Research Projects Agency (DOD...DATES COVERED (From - To! 4/14/2009-12/23/2009 4. TITLE AND SUBTITLE Exposing Latent Information in Folksonomies for Reasoning Sa. CONTRACT

  4. Polytomous latent scales for the investigation of the ordering of items

    NARCIS (Netherlands)

    Ligtvoet, R.; van der Ark, L.A.; Bergsma, W. P.; Sijtsma, K.

    2011-01-01

    We propose three latent scales within the framework of nonparametric item response theory for polytomously scored items. Latent scales are models that imply an invariant item ordering, meaning that the order of the items is the same for each measurement value on the latent scale. This ordering

  5. [Distribution of herpes simplex virus type 1 and 2 genomes in the human spinal ganglia].

    Science.gov (United States)

    Obara, Y

    1994-09-01

    Herpes simplex virus (HSV) is well known for its propensity to cause recurrent oral or genital mucosal infections in humans. HSV-1 is involved primarily in oral lesions, whereas HSV-2 is more frequently involved in genital lesions. Based on this, it is thought that HSV-1 may produce latent infections in trigeminal ganglia, and HSV-2 in the sacral ganglia. However the distribution pattern of latent HSV-1 and HSV-2 infections in spinal ganglia remains unknown. Using the polymerase chain reaction we detected latent herpes HSV-1 and HSV-2 in human spinal ganglia obtained from autopsy material. A pair of primers which were specific for a part of the HSV-1 and HSV-2 DNA polymerase domain were employed. HSV-1 and HSV-2 DNAs were detected in 11 of 40 (28%) and 15 of 40 (38%) cervical ganglia, respectively, 52 of 103 (50%) and 47 of 103 (46%) thoracic ganglia, 16 of 53 (30%) and 17 of 53 (32%) lumbar ganglia, and 3 of 20 (15%) and 3 of 20 (15%) sacral ganglia. These findings suggest that latent HSV-1 and HSV-2 infections have a widespread distribution from the cervical ganglia to sacral ganglia. Importantly this study demonstrated latent HSV-1 infection of both the lumbar and sacral ganglia for the first time.

  6. DNA immunization against experimental genital herpes simplex virus infection.

    Science.gov (United States)

    Bourne, N; Stanberry, L R; Bernstein, D I; Lew, D

    1996-04-01

    A nucleic acid vaccine, expressing the gene encoding herpes simplex virus (HSV) type 2 glycoprotein D (gD2) under control of the cytomegalovirus immediate-early gene promoter, was used to immunize guinea pigs against genital HSV-2 infection. The vaccine elicited humoral immune responses comparable to those seen after HSV-2 infection. Immunized animals exhibited protection from primary genital HSV-2 disease with little or no development of vesicular skin lesions and significantly reduced HSV-2 replication in the genital tract. After recovery from primary infection, immunized guinea pigs experienced significantly fewer recurrences and had significantly less HSV-2 genomic DNA detected in the sacral dorsal root ganglia compared with control animals. Thus, immunization reduced the burden of latent infection resulting from intravaginal HSV-2 challenge, and a nucleic acid vaccine expressing the HSV-2 gD2 antigen protected guinea pigs against genital herpes, limiting primary infection and reducing the magnitude of latent infection and the frequency of recurrent disease.

  7. Special Issue: Honey Bee Viruses

    Directory of Open Access Journals (Sweden)

    Sebastian Gisder

    2015-10-01

    Full Text Available Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus, or a so far neglected virus species (Apis mellifera filamentous virus, and cutting edge technologies (mass spectrometry, RNAi approach applied in the field.

  8. Special Issue: Honey Bee Viruses

    Science.gov (United States)

    Gisder, Sebastian; Genersch, Elke

    2015-01-01

    Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus), or a so far neglected virus species (Apis mellifera filamentous virus), and cutting edge technologies (mass spectrometry, RNAi approach) applied in the field. PMID:26702462

  9. Bayesian latent feature modeling for modeling bipartite networks with overlapping groups

    DEFF Research Database (Denmark)

    Jørgensen, Philip H.; Mørup, Morten; Schmidt, Mikkel Nørgaard

    2016-01-01

    Bi-partite networks are commonly modelled using latent class or latent feature models. Whereas the existing latent class models admit marginalization of parameters specifying the strength of interaction between groups, existing latent feature models do not admit analytical marginalization...... by the notion of community structure such that the edge density within groups is higher than between groups. Our model further assumes that entities can have different propensities of generating links in one of the modes. The proposed framework is contrasted on both synthetic and real bi-partite networks...... feature representations in bipartite networks provides a new framework for accounting for structure in bi-partite networks using binary latent feature representations providing interpretable representations that well characterize structure as quantified by link prediction....

  10. Latent Growth and Dynamic Structural Equation Models.

    Science.gov (United States)

    Grimm, Kevin J; Ram, Nilam

    2018-05-07

    Latent growth models make up a class of methods to study within-person change-how it progresses, how it differs across individuals, what are its determinants, and what are its consequences. Latent growth methods have been applied in many domains to examine average and differential responses to interventions and treatments. In this review, we introduce the growth modeling approach to studying change by presenting different models of change and interpretations of their model parameters. We then apply these methods to examining sex differences in the development of binge drinking behavior through adolescence and into adulthood. Advances in growth modeling methods are then discussed and include inherently nonlinear growth models, derivative specification of growth models, and latent change score models to study stochastic change processes. We conclude with relevant design issues of longitudinal studies and considerations for the analysis of longitudinal data.

  11. 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.

  12. Handbook of latent variable and related models

    CERN Document Server

    Lee, Sik-Yum

    2011-01-01

    This Handbook covers latent variable models, which are a flexible class of models for modeling multivariate data to explore relationships among observed and latent variables.- Covers a wide class of important models- Models and statistical methods described provide tools for analyzing a wide spectrum of complicated data- Includes illustrative examples with real data sets from business, education, medicine, public health and sociology.- Demonstrates the use of a wide variety of statistical, computational, and mathematical techniques.

  13. Increased pathogenicity and shedding in chickens of a wild bird-origin low pathogenicity avian influenza virus of the H7N3 subtype following multiple in vivo passages in quail and turkey.

    Science.gov (United States)

    Cilloni, Filippo; Toffan, Anna; Giannecchini, Simone; Clausi, Valeria; Azzi, Alberta; Capua, Ilaria; Terregino, Calogero

    2010-03-01

    In order to investigate viral adaptation mechanisms to poultry, we performed serial in vivo passages of a wild bird low pathogenicity avian influenza isolate of the H7N3 subtype (A/mallard/Italy/33/01) in three different domestic species (chicken, turkey, and Japanese quail). The virus under study was administered via natural routes at the dose of 10(6) egg infective dose50/ 0.1 ml to chickens, turkeys, and quails in order to investigate the clinical susceptibility and the shedding levels after infection. Multiple in vivo passages of the virus were performed by serially infecting groups of five naive birds of each species, with samples collected from a previously infected group. Quails and turkeys were susceptible to infection for 10 serial passages, whereas chickens were susceptible to two cycles of infection only. Infection of chicken with the quail- and turkey-adapted viruses showed an increased pathogenicity and/or shedding, causing more severe clinical signs and/or higher levels of viral excretion compared to the original strain. The data obtained herein suggest that infection of selected avian species may facilitate the adaptation of avian influenza viruses originating from the wild bird reservoir to chicken. This is the first time turkey has been shown to act as a species in which a virus from the wild reservoir can increase its replication activity in other domestic species.

  14. Aspects of physicochemical methods for the detection of latent fingerprints

    International Nuclear Information System (INIS)

    Knowles, A.M.

    1978-01-01

    This paper reviews physicochemical methods of detecting latent finger-prints on a wide range of materials commonly found at the scene of a crime, with particular emphasis placed on the newer autoradiographic techniques. This is set against a description of studies on the fundamental nature of the latent fingerprint and its host substrate, with a brief review of the history of reagents used in latent fingerprint examination. (author)

  15. Characterization of a siberian virus isolated from a patient with progressive chronic tick-borne encephalitis.

    Science.gov (United States)

    Gritsun, T S; Frolova, T V; Zhankov, A I; Armesto, M; Turner, S L; Frolova, M P; Pogodina, V V; Lashkevich, V A; Gould, E A

    2003-01-01

    A strain of Tick-borne encephalitis virus designated Zausaev (Za) was isolated in Siberia from a patient who died of a progressive (2-year) form of tick-borne encephalitis 10 years after being bitten by a tick. The complete genomic sequence of this virus was determined, and an attempt was made to correlate the sequence with the biological characteristics of the virus. Phylogenetic analysis demonstrated that this virus belongs to the Siberian subtype of Tick-borne encephalitis virus. Comparison of Za virus with two related viruses, a Far Eastern isolate, Sofjin, and a Siberian isolate, Vasilchenko, revealed differences among the three viruses in pathogenicity for Syrian hamsters, cytopathogenicity for PS cells, plaque morphology, and the electrophoretic profiles of virus-specific nonstructural proteins. Comparative amino acid alignments revealed 10 individual amino acid substitutions in the Za virus polyprotein sequence that were different from those of other tick-borne flaviviruses. Notably, the dimeric form of the Za virus NS1 protein migrated in polyacrylamide gels as a heterogeneous group of molecules with a significantly higher electrophoretic mobility than those of the Sofjin and Vasilchenko viruses. Two amino acid substitutions, T(277)-->V and E(279)-->G, within the NS1 dimerization domain are probably responsible for the altered oligomerization of Za virus NS1. These studies suggest that the patient from whom Za virus was isolated died due to increased pathogenicity of the latent virus following spontaneous mutagenesis.

  16. Latent M. tuberculosis infection--pathogenesis, diagnosis, treatment and prevention strategies.

    Science.gov (United States)

    Druszczyńska, Magdalena; Kowalewicz-Kulbat, Magdalena; Fol, Marek; Włodarczyk, Marcin; Rudnicka, Wiesława

    2012-01-01

    One third of the earths population is infected with Mycobacterium tuberculosis (Mtb), but only 5-10% of the infected individuals develop active tuberculosis (TB) over their lifetime. The remaining 90-95% stay healthy and are called latently infected individuals. They are the biggest reservoir of the tubercle bacilli and identifying the cases of latent TB is a part of the global plan of TB control. From the clinical point of view detection of latent TB infections (LTBI) in individuals with the highest active TB risk including cases of HIV infection, autoimmune inflammatory diseases or cancer, is a priority. This review summarizes the recent findings in the pathogenesis of latent TB, its diagnosis, treatment and prevention.

  17. Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis.

    Science.gov (United States)

    Giudice, Aldo; D'Arena, Giovanni; Crispo, Anna; Tecce, Mario Felice; Nocerino, Flavia; Grimaldi, Maria; Rotondo, Emanuela; D'Ursi, Anna Maria; Scrima, Mario; Galdiero, Massimiliano; Ciliberto, Gennaro; Capunzo, Mario; Franci, Gianluigi; Barbieri, Antonio; Bimonte, Sabrina; Montella, Maurizio

    2016-01-01

    MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs.

  18. Herpes simplex virus type 1-derived recombinant and amplicon vectors.

    Science.gov (United States)

    Fraefel, Cornel; Marconi, Peggy; Epstein, Alberto L

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153 kbp double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes (1) the two approaches most commonly used to prepare recombinant vectors through homologous recombination, either in eukaryotic cells or in bacteria, and (2) the two methodologies currently used to generate helper-free amplicon vectors, either using a bacterial artificial chromosome (BAC)-based approach or a Cre/loxP site-specific recombination strategy.

  19. Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of negative-sense RNA viruses.

    Science.gov (United States)

    Li, Ci-Xiu; Shi, Mang; Tian, Jun-Hua; Lin, Xian-Dan; Kang, Yan-Jun; Chen, Liang-Jun; Qin, Xin-Cheng; Xu, Jianguo; Holmes, Edward C; Zhang, Yong-Zhen

    2015-01-29

    Although arthropods are important viral vectors, the biodiversity of arthropod viruses, as well as the role that arthropods have played in viral origins and evolution, is unclear. Through RNA sequencing of 70 arthropod species we discovered 112 novel viruses that appear to be ancestral to much of the documented genetic diversity of negative-sense RNA viruses, a number of which are also present as endogenous genomic copies. With this greatly enriched diversity we revealed that arthropods contain viruses that fall basal to major virus groups, including the vertebrate-specific arenaviruses, filoviruses, hantaviruses, influenza viruses, lyssaviruses, and paramyxoviruses. We similarly documented a remarkable diversity of genome structures in arthropod viruses, including a putative circular form, that sheds new light on the evolution of genome organization. Hence, arthropods are a major reservoir of viral genetic diversity and have likely been central to viral evolution.

  20. Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?

    Science.gov (United States)

    Al-Dujaili, Lena J; Clerkin, Patrick P; Clement, Christian; McFerrin, Harris E; Bhattacharjee, Partha S; Varnell, Emily D; Kaufman, Herbert E; Hill, James M

    2012-01-01

    Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases. PMID:21861620

  1. Transmission of Avian Influenza Virus (H3N2) to Dogs

    OpenAIRE

    Song, Daesub; Kang, Bokyu; Lee, Chulseung; Jung, Kwonil; Ha, Gunwoo; Kang, Dongseok; Park, Seongjun; Park, Bongkyun; Oh, Jinsik

    2008-01-01

    In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) is...

  2. [Herpes simplex virus and malignancies of female genital organs].

    Science.gov (United States)

    Cokić-Damjanović, J; Horvat, E; Balog, A

    2001-01-01

    Primary herpes simplex virus (HSV) infections of female genital tract usually end with remission, while the virus remains in the organism--almost in the sacral ganglion in a latent form, protected from humoral and cellular immunity. Stress induces the virus and the result is recurrent genital infection. Frequent exacerbations damage some parts of vital cellular structures without cytolysis, but stimulate malignant transformations. Vulvar (portio vaginalis uteri) and endometrial tumor tissue samples were analyzed for HSV by direct and indirect fluorescent antibody technique (FAT). Pre and postoperative sera samples were analyzed for presence of anti-HSV antibodies--IgM and IgG by Elisa-Enzygnost method. Acellular filtrates obtained by ultrasonic destruction of malignant tissues were used as inoculum for rabbit corneal scarification. Out of 63 tissue samples, 42 were positive for HSV antigen i.e. 67.3%. According to location 50% of vulvar, 76% PVU and 65% of endometrial tissues were positive. This antigen induces production of virus specific antibodies. Two types of antigens are known: the so-called T-antigen persisting in the cell nucleus and cell-surface antigen--product of the viral genome and can be evidenced by immunofluorescence method. Anti HSV antibodies were present in 63 preoperative serum samples and belonged to IgG group, but not one to IgM, implying a long and chronic course of infection excluding acute primary. Out of 38 postoperative serums the titer of antibodies decreased in 36 evidently, but in two samples remained unchanged. Two samples of endometrial and one from PVU origin contained HSV antigen type one. In the remaining 16 samples HSV 2 antigen was present. Rabbit corneal scarification was the proof of complete infectious virus in malignant tissues. Acellular filtrate of malignant tissues served as inoculum. Corneas of examined rabbits showed a mild inflammation after 24 hours which disappeared in the next 24 hours. We could not isolate the

  3. Clinical and epidemiologic characteristics of an outbreak of novel H1N1 (swine origin) influenza A virus among United States military beneficiaries.

    Science.gov (United States)

    Crum-Cianflone, Nancy F; Blair, Patrick J; Faix, Dennis; Arnold, John; Echols, Sara; Sherman, Sterling S; Tueller, John E; Warkentien, Tyler; Sanguineti, Gabriela; Bavaro, Mary; Hale, Braden R

    2009-12-15

    A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts. We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15-25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%-14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths. A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young

  4. Sibling Relationship Quality and Mexican-Origin Adolescents' and Young Adults' Familism Values and Adjustment

    Science.gov (United States)

    Killoren, Sarah E.; De Jesús, Sue A. Rodríguez; Updegraff, Kimberly A.; Wheeler, Lorey A.

    2017-01-01

    We examined profiles of sibling relationship qualities in 246 Mexican-origin families living in the United States using latent profile analyses. Three profiles were identified: "Positive," "Negative," and "Affect-Intense." Links between profiles and youths' familism values and adjustment were assessed using…

  5. Mutations Inactivating Herpes Simplex Virus 1 MicroRNA miR-H2 Do Not Detectably Increase ICP0 Gene Expression in Infected Cultured Cells or Mouse Trigeminal Ganglia.

    Science.gov (United States)

    Pan, Dongli; Pesola, Jean M; Li, Gang; McCarron, Seamus; Coen, Donald M

    2017-01-15

    Herpes simplex virus 1 (HSV-1) latency entails the repression of productive ("lytic") gene expression. An attractive hypothesis to explain some of this repression involves inhibition of the expression of ICP0, a lytic gene activator, by a viral microRNA, miR-H2, which is completely complementary to ICP0 mRNA. To test this hypothesis, we engineered mutations that disrupt miR-H2 without affecting ICP0 in HSV-1. The mutant virus exhibited drastically reduced expression of miR-H2 but showed wild-type levels of infectious virus production and no increase in ICP0 expression in lytically infected cells, which is consistent with the weak expression of miR-H2 relative to the level of ICP0 mRNA in that setting. Following corneal inoculation of mice, the mutant was not significantly different from wild-type virus in terms of infectious virus production in the trigeminal ganglia during acute infection, mouse mortality, or the rate of reactivation from explanted latently infected ganglia. Critically, the mutant was indistinguishable from wild-type virus for the expression of ICP0 and other lytic genes in acutely and latently infected mouse trigeminal ganglia. The latter result may be related to miR-H2 being less effective in inhibiting ICP0 expression in transfection assays than a host microRNA, miR-138, which has previously been shown to inhibit lytic gene expression in infected ganglia by targeting ICP0 mRNA. Additionally, transfected miR-138 reduced lytic gene expression in infected cells more effectively than miR-H2. While this study provides little support for the hypothesis that miR-H2 promotes latency by inhibiting ICP0 expression, the possibility remains that miR-H2 might target other genes during latency. Herpes simplex virus 1 (HSV-1), which causes a variety of diseases, can establish lifelong latent infections from which virus can reactivate to cause recurrent disease. Latency is the most biologically interesting and clinically vexing feature of the virus. Ever since

  6. Does a feline leukemia virus infection pave the way for Bartonella henselae infection in cats?

    Science.gov (United States)

    Buchmann, Alexandra U; Kershaw, Olivia; Kempf, Volkhard A J; Gruber, Achim D

    2010-09-01

    Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in cats-Feline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)-on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence.

  7. Towards an HIV-1 cure: measuring the latent reservoir

    Science.gov (United States)

    Bruner, Katherine M.; Hosmane, Nina N.; Siliciano, Robert F.

    2015-01-01

    The latent reservoir of HIV-1 in resting memory CD4+ T cells serves as a major barrier to curing HIV-1 infection. While many PCR- and culture-based assays have been used to measure the size of the latent reservoir, correlation between results of different assays is poor and recent studies indicate that no available assay provides an accurate measurement of reservoir size. The discrepancies between assays are a hurdle to clinical trials that aim to measure the efficacy of HIV-1 eradication strategies. Here we describe the advantages and disadvantages of various approaches to measure the latent reservoir. PMID:25747663

  8. Study of noninvasive detection of latent fingerprints using UV laser

    Science.gov (United States)

    Li, Hong-xia; Cao, Jing; Niu, Jie-qing; Huang, Yun-gang; Mao, Lin-jie; Chen, Jing-rong

    2011-06-01

    Latent fingerprints present a considerable challenge in forensics, and noninvasive procedure that captures a digital image of the latent fingerprints is significant in the field of criminal investigation. The capability of photography technologies using 266nm UV Nd:YAG solid state laser as excitation light source to provide detailed images of unprocessed latent fingerprints is demonstrated. Unprocessed latent fingerprints were developed on various non-absorbent and absorbing substrates. According to the special absorption, reflection, scattering and fluorescence characterization of the various residues in fingerprints (fatty acid ester, protein, and carbosylic acid salts etc) to the UV light to weaken or eliminate the background disturbance and increase the brightness contrast of fingerprints with the background, and using 266nm UV laser as excitation light source, fresh and old latent fingerprints on the surface of four types of non-absorbent objects as magazine cover, glass, back of cellphone, wood desktop paintwork and two types of absorbing objects as manila envelope, notebook paper were noninvasive detected and appeared through reflection photography and fluorescence photography technologies, and the results meet the fingerprint identification requirements in forensic science.

  9. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.

    Science.gov (United States)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J

    2009-11-12

    Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.

  10. Latent tuberculosis in nursing professionals of a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Valim Andréia

    2011-05-01

    Full Text Available Abstract Tuberculosis (TB is considered an occupational disease among health-care workers (HCWs. Direct contact with TB patients leads to an increased risk to become latently infected by Mycobacterium tuberculosis. The objective of this study is to estimate the prevalence of latent M. tuberculosis minfection among nursing professionals of a hospital in Rio Grande do Sul, Brazil, assessed by tuberculin skin test (TST. From November 2009 to May 2010, latent M. tuberculosis infection was assessed by TST in 55 nursing professionals. Epidemiological information was collected using a standardized questionnaire. A positive TST result (> or = 10 mm was observed in 47.3% of the HCWs tested. There was no significant difference in TST positivity when duration of employment or professional category (technician or nurse was evaluated. The results of this work reinforce the need for control measures to prevent latent M. tuberculosis infection among nursing professionals at the hospital where the study was conducted.

  11. Immunogenicity of peptides of measles virus origin and influence of adjuvants.

    Science.gov (United States)

    Halassy, Beata; Mateljak, Sanja; Bouche, Fabienne B; Pütz, Mike M; Muller, Claude P; Frkanec, Ruza; Habjanec, Lidija; Tomasić, Jelka

    2006-01-12

    Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.

  12. Complete sequence of Fig fleck-associated virus, a novel member of the family Tymoviridae.

    Science.gov (United States)

    Elbeaino, Toufic; Digiaro, Michele; Martelli, Giovanni P

    2011-11-01

    The complete nucleotide sequence and the genome organization were determined of a novel virus, tentatively named Fig fleck-associated virus (FFkaV). The viral genome is a positive-sense, single-stranded RNA 7046 nucleotides in size excluding the 3'-terminal poly(A) tract, and comprising two open reading frames. ORF1 encodes a polypeptide of 2161 amino acids (p240), which contains the signatures of replication-associated proteins and the coat protein cistron (p24) at its 3' end. ORF2 codes for a 461 amino acid protein (p50) identified as a putative movement proteins (MP). In phylogenetic trees constructed with sequences of the putative polymerase and CP proteins FFkaV consistently groups with members of the genus Maculavirus, family Tymoviridae. However, the genome organization diverges from that of the two completely sequenced maculaviruses, Grapevine fleck virus (GFkV) and Bombix mori Macula-like virus (BmMLV), as it exhibits a structure resembling that of Maize rayado fino virus (MRFV), the type species of the genus Marafivirus and of Olive latent virus 3 (OLV-3), an unclassified virus in the family Tymoviridae. FFkaV was found in field-grown figs from six Mediterranean countries with an incidence ranging from 15% to 25%. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

    Science.gov (United States)

    Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

    2018-06-01

    Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

  14. Primiparous women's preferences for care during a prolonged latent phase of labour.

    Science.gov (United States)

    Ängeby, Karin; Wilde-Larsson, Bodil; Hildingsson, Ingegerd; Sandin-Bojö, Ann-Kristin

    2015-10-01

    To investigate primiparous women's preferences for care during a prolonged latent phase of labour. A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Aspectos virológicos e clínico-patológicos da infecção genital aguda e latente pelo herpesvírus bovino tipo 1.2 em bezerras infectadas experimentalmente Virological and clinico-pathological features of acute vulvovaginitis and latent infection by bovine herpesvirus 1.2 in heifers experimentally infected

    Directory of Open Access Journals (Sweden)

    Andréia Henzel

    2008-03-01

    and cows with bovine herpesvirus type 1.2 (BoHV-1.2 may result in vulvovaginitis and transient infertility. The acute infection is followed by the establishment of latent infection which can be periodically reactivated. We herein describe the virology and clinico-pathological aspects of acute and recrudescent vulvovaginitis in heifers inoculated with a Brazilian BoHV-1.2 isolate recovered from an outbreak of balanoposthitis. Genital inoculation of isolate SV-56/90 (10(8.1TCID50/animal in four eight-months-old heifers resulted in efficient virus replication in the genital mucosa and the development of moderate to severe vulvovaginitis. The inoculated heifers shed virus in genital secretions in titers up to 10(7.3TCID50/mL until day 10 pi and developed genital congestion, swelling, vesicles and pustules. The vesicles and pustules increased in size eventually coalesced and became covered with a yellowish exsudate. These signs appeared at day 2 pi, increased in severity up to days 5 - 8 pi and progressively subsided thereafter. Dexamethasone administration at day 55 pi resulted in virus shedding in vaginal secretions for up to 10 days. Virus reactivation in all animals was accompanied by clinical recrudescence of the disease, yet less severe than during acute infection. Examination of sacral ganglia and lymph nodes by PCR at day 36 post-reactivation revealed the presence of latent viral DNA in the pudendal (4/4, genito-femoral, sciatic and rectal caudal (3/4 and obturator nerve ganglia (1/4; in addition to several regional lymph nodes. These results demonstrate the virulence of isolate SV-56/90 for heifers and pave the way for its use in further pathogenesis studies and vaccine-challenge trials.

  16. Online social networks—Paradise of computer viruses

    Science.gov (United States)

    Fan, W.; Yeung, K. H.

    2011-01-01

    Online social network services have attracted more and more users in recent years. So the security of social networks becomes a critical problem. In this paper, we propose a virus propagation model based on the application network of Facebook, which is the most popular among these social network service providers. We also study the virus propagation with an email virus model and compare the behaviors of a virus spreading on Facebook with the original email network. It is found that Facebook provides the same chance for a virus spreading while it gives a platform for application developers. And a virus will spread faster in the Facebook network if users of Facebook spend more time on it.

  17. Gene variants associated with antisocial behaviour: a latent variable approach.

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V; Lee, Maria; Yrigollen, Carolyn M; Pakstis, Andrew J; Katsovich, Liliya; Olds, David L; Grigorenko, Elena L; Leckman, James F

    2013-10-01

    The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential 'co-action' of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a

  18. Tratamento da tuberculose de infecção latente: As recomendações actuais Latent tuberculosis infection treatment: Current recommendations

    Directory of Open Access Journals (Sweden)

    R Duarte

    2010-09-01

    Full Text Available O diagnóstico e tratamento da infecção latente por Mycobacterium tuberculosis reduz significativamente o risco de desenvolvimento de tuberculose activa e a transmissão da doença na comunidade. O rastreio da tuberculose infecção latente deve passar pela exclusão de doença activa (inquérito de sintomas e radiografia pulmonar e avaliação da resposta imunológica ao M. tuberculosis através dos testes actualmente ao dispor, como o teste tuberculínico e os testes IGRA (interferon-gamma release assay. A escolha do esquema de tratamento deve ter em linha de conta a eficácia, a adesão e os efeitos colaterais associados ao mesmo Este documento actualiza as recomendações sobre tratamento da tuberculose infecção latente. São apresentadas indicações sobre quem deve ser rastreado e revistos os esquemas de tratamento.Diagnosis and treatment of latent infection with Mycobacterium tuberculosis (LTBI, significantly reduces the risk of developing active tuberculosis and the transmission of the disease in the community. LTBI screening must pass by the exclusion of active disease (symptoms enquiry and chest radiography and assessment of immune response to Mycobacterium tuberculosis testing with the tests currently available - tuberculin skin test and interferon-gamma release assay (IGRA. The choice of treatment must take into account the efficacy and side effects associated with the same. This document provides updated recommendations on latent tuberculosis infection treatment. Topics covered include whom to test for TB and reviewed LTBI treatment regimens.

  19. Calculating latent frequencies of systems with local damping

    International Nuclear Information System (INIS)

    Kolonits, Ferenc

    2005-01-01

    Modal analysis of damped systems often cannot proceed with common real-eigenvalue techniques. The system of equilibrium equations leads to a matrix with elements being quadratic functions of a parameter λ. The values of that which make the matrix singular are the latent roots, while the solutions of the associated homogenous equation are the latent vectors. They are the (generally complex) characteristic frequencies and the mode shapes of the system, respectively. Although the theory is well developed, the numerical application is open to refinements yet. A reduction to better-known real-domain subtasks deserves attention. With a theorem of Popper and Gaspar, a n x n λ-matrix problem can be cut in two: into n-size asymmetric real matrices having as eigenvalues the n lower and n upper latent roots, ranked by absolute value. This approach may be of use for systems with high number of degrees of freedom while damped by a relatively few concentrated devices. It might fit also an earthquake analysis, where the lower portion of eigenvalues is customarily what counts. The dampers appear in the splitting algorithm as restricted-size modifications, ready for use by the Sherman-Morrison-Woodbury identity. The task is re-traced this way to a more usual real-asymmetric eigenproblem. A requirement of convergence is that the lower and upper n-set of latent values must be distinct. With odd-number degrees of freedom and neither over-damped, i.e. all latent roots being complex, this condition is surely violated. For such cases, a supplemental algorithm is proposed

  20. Behaviorism, latent learning, and cognitive maps: needed revisions in introductory psychology textbooks.

    Science.gov (United States)

    Jensen, Robert

    2006-01-01

    This paper critically assesses the scholarship in introductory psychology textbooks in relation to the topic of latent learning. A review of the treatment of latent learning in 48 introductory psychology textbooks published between 1948 and 2004, with 21 of these texts published since 1999, reveals that the scholarship on the topic of latent learning demonstrated in introductory textbooks warrants improvement. Errors that persist in textbooks include the assertion that the latent learning experiments demonstrate unequivocally that reinforcement was not necessary for learning to occur, that behavioral theories could not account for the results of the latent learning experiments, that B. F. Skinner was an S-R association behaviorist who argued that reinforcement is necessary for learning to occur, and that because behavioral theories (including that of B. F. Skinner) were unable explain the results of the latent learning experiments the cognitive map invoked by Edward Tolman is the only explanation for latent learning. Finally, the validity of the cognitive map is typically accepted without question. Implications of the presence of these errors for students and the discipline are considered. Lastly, remedies are offered to improve the scholarship found in introductory psychology textbooks.

  1. Generalized latent variable modeling multilevel, longitudinal, and structural equation models

    CERN Document Server

    Skrondal, Anders; Rabe-Hesketh, Sophia

    2004-01-01

    This book unifies and extends latent variable models, including multilevel or generalized linear mixed models, longitudinal or panel models, item response or factor models, latent class or finite mixture models, and structural equation models.

  2. Latent Class Analysis of Criminal Social Identity in a Prison Sample

    Directory of Open Access Journals (Sweden)

    Boduszek Daniel

    2014-06-01

    Full Text Available This study aimed to examine the number of latent classes of criminal social identity that exist among male recidivistic prisoners. Latent class analysis was used to identify homogeneous groups of criminal social identity. Multinomial logistic regression was used to interpret the nature of the latent classes, or groups, by estimating the associationsto number of police arrests, recidivism, and violent offending while controlling for current age. The best fitting latent class model was a five-class solution: ‘High criminal social identity’ (17%, ‘High Centrality, Moderate Affect, Low Ties’ (21.7%, ‘Low Centrality, Moderate Affect, High Ties’ (13.3%,‘Low Cognitive, High Affect, Low Ties’ (24.6%, and ‘Low criminal social identity’ (23.4%. Each of the latent classes was predicted by differing external variables. Criminal social identity is best explained by five homogenous classes that display qualitative and quantitative differences.

  3. Neurons versus herpes simplex virus: the innate immune interactions that contribute to a host–pathogen standoff

    Science.gov (United States)

    Rosato, Pamela C; Leib, David A

    2015-01-01

    Herpes simplex virus (HSV) is a prevalent neurotropic virus, which establishes lifelong latent infections in the neurons of sensory ganglia. Despite our long-standing knowledge that HSV predominately infects sensory neurons during its life cycle, little is known about the neuronal antiviral response to HSV infection. Recent studies show that while sensory neurons have impaired intrinsic immunity to HSV infection, paracrine IFN signaling can potentiate a potent antiviral response. Additionally, antiviral autophagy plays an important role in neuronal control of HSV infection. Here we review the literature of antiviral signaling and autophagy in neurons, the mechanisms by which HSV can counteract these responses, and postulate how these two pathways may synergize to mediate neuronal control of HSV infection and yet result in lifelong persistence of the virus. PMID:26213562

  4. Current management options for latent tuberculosis: a review

    Directory of Open Access Journals (Sweden)

    Norton BL

    2012-11-01

    Full Text Available Brianna L Norton, David P HollandDepartment of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USAAbstract: Tuberculosis remains the world’s second leading infectious cause of death, with nearly one-third of the global population latently infected. Treatment of latent tuberculosis infection is a mainstay of tuberculosis-control efforts in low-to medium-incidence countries. Isoniazid monotherapy has been the standard of care for decades, but its utility is impaired by poor completion rates. However, new, shorter-course regimens using rifamycins improve completion rates and are cost-saving compared with standard isoniazid monotherapy. We review the currently available therapies for latent tuberculosis infection and their toxicities and include a brief economic comparison of the different regimens.Keywords: isoniazid, rifampin, rifapentine, tuberculin skin test, interferon-gamma release assay

  5. Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys.

    Science.gov (United States)

    Slomka, Marek J; Seekings, Amanda H; Mahmood, Sahar; Thomas, Saumya; Puranik, Anita; Watson, Samantha; Byrne, Alexander M P; Hicks, Daniel; Nunez, Alejandro; Brown, Ian H; Brookes, Sharon M

    2018-05-09

    The China-origin H7N9 low pathogenicity avian influenza virus (LPAIV) emerged as a zoonotic threat in 2013 where it continues to circulate in live poultry markets. Absence of overt clinical signs in poultry is a typical LPAIV infection outcome, and has contributed to its insidious maintenance in China. This study is the first description of H7N9 LPAIV (A/Anhui/1/13) infection in turkeys, with efficient transmission to two additional rounds of introduced contact turkeys which all became infected during cohousing. Surprisingly, mortality was observed in six of eight (75%) second-round contact turkeys which is unusual for LPAIV infection, with unexpected systemic dissemination to many organs beyond the respiratory and enteric tracts, but interestingly no accompanying mutation to highly pathogenic AIV. The intravenous pathogenicity index score for a turkey-derived isolate (0.39) affirmed the LPAIV phenotype. However, the amino acid change L235Q in the haemagglutinin gene occurred in directly-infected turkeys and transmitted to the contacts, including those that died and the two which resolved infection to survive to the end of the study. This polymorphism was indicative of a reversion from mammalian to avian adaptation for the H7N9 virus. This study underlined a new risk to poultry in the event of H7N9 spread beyond China.

  6. Herpes virus production as a marker of repair in ultraviolet irradiated human skin cells of different origin

    Energy Technology Data Exchange (ETDEWEB)

    Coppey, J; Nocentini, S [Institut du Radium, 75 - Paris (France); Moreno, G [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital de Bicetre, 94 - le Kremlin-Bicetre (France)

    1978-01-01

    When confluent human skin cultures are ultraviolet (UV)-irradiated before infection with Herpes Simplex type 1 virus (HSV), their capacity to support virus growth is impaired. When the time interval between UV-exposure and infection is increased up to 36 hours, different recoveries of HSV production capacity are observed according to the origin of the host cells. 1) Two normal donors: the cells present a dose dependent recovery which is maximal for a dose (24 J/m/sup 2/) at which a plateau level of unscheduled DNA synthesis (UDS) is reached. 2) A mother of two Xeroderma Pigmentosum (XP) children: in this line which exhibits a normal level of UDS, the extent of recovery is significantly decreased after exposures <=12 J/m/sup 2/. 3) An XP child: these cells have a normal level of UDS (XP variant) whereas they present a low extent of recovery as compared with that of the normal subjects. 4) Five XP children: in these excision deficient lines (UDS < 15%), HSV production capacity decreases with increasing time intervals after UV exposure for doses >=3 J/m/sup 2/. For doses < 3 J/m/sup 2/, a small recovery with an overshoot of viral production is observed 24 h after UV exposure in the lines (three) which present the highest UDS (10-15%) and not in the two lines which present a very low UDS (1-2%).

  7. Evolutionary insights from studies on viruses of hyperthermophilic archaea.

    Science.gov (United States)

    Prangishvili, David

    2003-05-01

    The morphological diversity of viruses which parasitize hyperthermophilic archaea thriving at temperatures > or = 80 degrees C appears to exceed that of viruses of prokaryotes living at lower temperatures. Based on assumptions of the existence of viruses in the prebiotic phase of evolution and hot origins of cellular life, we suggest that this remarkable diversity could have its source in ancestral diversity of viral morphotypes in hot environments. Attempts are made to trace evolutionary relationships of viruses of hyperthermophilic archaea with other viruses.

  8. Harry Potter and the sorcerer's scope: latent scope biases in explanatory reasoning.

    Science.gov (United States)

    Khemlani, Sangeet S; Sussman, Abigail B; Oppenheimer, Daniel M

    2011-04-01

    What makes a good explanation? We examine the function of latent scope, i.e., the number of unobserved phenomena that an explanation can account for. We show that individuals prefer narrow latent scope explanations-those that account for fewer unobserved effects-to broader explanations. In Experiments 1a-d, participants found narrow latent scope explanations to be both more satisfying and more likely. In Experiment 2 we directly manipulated base rate information and again found a preference for narrow latent scope explanations. Participants in Experiment 3 evaluated more natural explanations of unexpected observations, and again displayed a bias for narrow latent scope explanations. We conclude by considering what this novel bias tells us about how humans evaluate explanations and engage in causal reasoning.

  9. Mexican-Origin Mothers' and Fathers' Involvement in Adolescents' Peer Relationships: A Pattern-Analytic Approach

    Science.gov (United States)

    Updegraff, Kimberly A.; Perez-Brena, Norma J.; Baril, Megan E.; McHale, Susan M.; Umana-Taylor, Adriana J.

    2012-01-01

    Using latent profile analysis, the authors examined patterns of mother-father involvement in adolescents' peer relationships along three dimensions--support, guidance, and restrictions--in 240 Mexican-origin families. Three profiles were identified: (a) High Mother Involvement (mothers higher than fathers on all three dimensions), (b) High…

  10. Genital herpes simplex virus infection: clinical course and attempted therapy.

    Science.gov (United States)

    Davis, L G; Keeney, R E

    1981-06-01

    The epidemiology, clinical course, diagnosis, and attempted treatments of herpes genitalis are reviewed. Herpes genitalis is an increasingly common sexually transmitted disease for which there is no effective treatment. It can occur in either sex and is mot commonly first found in patients 14 to 29 years old. Initial exposure to the virus may result in prolonged local symptoms (pain, itching, discharge) and signs (ulcerative lesions) as well as fever, malaise, myalgias, and fatigue. After the initial exposure, the virus may be found in a latent stage in the dorsal nerve root ganglia in the sacral area, and recurrences of disease may ensue. The frequency and clinical course of recurrent genital herpes can be of varying duration and severity. Although antiviral substances, immune potentiators, topical surfactants, and photodynamic inactivation have been used to treat genital herpes infections, there is no proven effective therapy.

  11. The ancient Virus World and evolution of cells

    Directory of Open Access Journals (Sweden)

    Dolja Valerian V

    2006-09-01

    Full Text Available Abstract Background Recent advances in genomics of viruses and cellular life forms have greatly stimulated interest in the origins and evolution of viruses and, for the first time, offer an opportunity for a data-driven exploration of the deepest roots of viruses. Here we briefly review the current views of virus evolution and propose a new, coherent scenario that appears to be best compatible with comparative-genomic data and is naturally linked to models of cellular evolution that, from independent considerations, seem to be the most parsimonious among the existing ones. Results Several genes coding for key proteins involved in viral replication and morphogenesis as well as the major capsid protein of icosahedral virions are shared by many groups of RNA and DNA viruses but are missing in cellular life forms. On the basis of this key observation and the data on extensive genetic exchange between diverse viruses, we propose the concept of the ancient virus world. The virus world is construed as a distinct contingent of viral genes that continuously retained its identity throughout the entire history of life. Under this concept, the principal lineages of viruses and related selfish agents emerged from the primordial pool of primitive genetic elements, the ancestors of both cellular and viral genes. Thus, notwithstanding the numerous gene exchanges and acquisitions attributed to later stages of evolution, most, if not all, modern viruses and other selfish agents are inferred to descend from elements that belonged to the primordial genetic pool. In this pool, RNA viruses would evolve first, followed by retroid elements, and DNA viruses. The Virus World concept is predicated on a model of early evolution whereby emergence of substantial genetic diversity antedates the advent of full-fledged cells, allowing for extensive gene mixing at this early stage of evolution. We outline a scenario of the origin of the main classes of viruses in conjunction

  12. Dynamic Latent Classification Model

    DEFF Research Database (Denmark)

    Zhong, Shengtong; Martínez, Ana M.; Nielsen, Thomas Dyhre

    as possible. Motivated by this problem setting, we propose a generative model for dynamic classification in continuous domains. At each time point the model can be seen as combining a naive Bayes model with a mixture of factor analyzers (FA). The latent variables of the FA are used to capture the dynamics...

  13. The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to promote the accumulation of SUMO conjugates and the release of infectious virus.

    Science.gov (United States)

    Li, Jinlin; Callegari, Simone; Masucci, Maria G

    2017-04-01

    Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) regulates a variety of cellular functions, and is hijacked by viruses to remodel the host cell during latent and productive infection. Here we have monitored the activity of the SUMO conjugation machinery in cells productively infected with Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the late phase of the productive virus cycle, and identified several viral proteins as bone fide SUMOylation substrates. Analysis of the mechanism involved in the accumulation of SUMOylated proteins revealed upregulation of several components of the SUMO-conjugation machinery and post-transcriptional downregulation of the SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1 resistant RNF4 was associated with reduced levels of early and late viral proteins and impaired virus release. These findings illustrate a novel strategy for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1 and the cellular RNF4 as regulators of the productive virus cycle.

  14. The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to promote the accumulation of SUMO conjugates and the release of infectious virus.

    Directory of Open Access Journals (Sweden)

    Jinlin Li

    2017-04-01

    Full Text Available Post-translational modification by the Small Ubiquitin-like Modifier (SUMO regulates a variety of cellular functions, and is hijacked by viruses to remodel the host cell during latent and productive infection. Here we have monitored the activity of the SUMO conjugation machinery in cells productively infected with Epstein-Barr virus (EBV. We found that SUMO2/3 conjugates accumulate during the late phase of the productive virus cycle, and identified several viral proteins as bone fide SUMOylation substrates. Analysis of the mechanism involved in the accumulation of SUMOylated proteins revealed upregulation of several components of the SUMO-conjugation machinery and post-transcriptional downregulation of the SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1 resistant RNF4 was associated with reduced levels of early and late viral proteins and impaired virus release. These findings illustrate a novel strategy for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1 and the cellular RNF4 as regulators of the productive virus cycle.

  15. A Latent Class Approach to Estimating Test-Score Reliability

    Science.gov (United States)

    van der Ark, L. Andries; van der Palm, Daniel W.; Sijtsma, Klaas

    2011-01-01

    This study presents a general framework for single-administration reliability methods, such as Cronbach's alpha, Guttman's lambda-2, and method MS. This general framework was used to derive a new approach to estimating test-score reliability by means of the unrestricted latent class model. This new approach is the latent class reliability…

  16. A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer

    International Nuclear Information System (INIS)

    Oh, Sang Taek; Seo, Jung Seon; Moon, Uk Yeol; Kang, Kyeong Hee; Shin, Dong-Jik; Yoon, Sungjoo Kim; Kim, Woo Ho; Park, Jae-Gahb; Lee, Suk Kyeong

    2004-01-01

    In a process seeking out a good model cell line for Epstein-Barr virus (EBV)-associated gastric cancer, we found that one previously established gastric adenocarcinoma cell line is infected with type 1 EBV. This SNU-719 cell line from a Korean patient expressed cytokeratin without CD19 or CD21 expression. In SNU-719, EBNA1 and LMP2A were expressed, while LMP1 and EBNA2 were not. None of the tested lytic EBV proteins were detected in this cell line unless stimulated with phorbol ester. EBV infection was also shown in the original carcinoma tissue of SNU-719 cell line. Our results support the possibility of a CD21-independent EBV infection of gastric epithelial cells in vivo. As the latent EBV gene expression pattern of SNU-719 closely resembles that of the EBV-associated gastric cancer, this naturally derived cell line may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis

  17. [Production of monoclonal antibodies against a wild strain of rabies virus].

    Science.gov (United States)

    Akacem, O; Benmansour, A; Coulon, P; Brahimi, M; Benhassine, M

    1992-01-01

    Production of monoclonal antibodies against a wild strain of rabies virus. Cell fusion of SP 2/O, a murine myeloma against a wild strain of rabies virus has originated five monoclonal antibodies (M.A.) specific for virus nucleocapsid , one M.A. specific for virus glycoprotein and one M.A. specific for a viral membrane protein.

  18. Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.

    Science.gov (United States)

    Agaya, Janet; Nnadi, Chimeremma D; Odhiambo, Joseph; Obonyo, Charles; Obiero, Vincent; Lipke, Virginia; Okeyo, Elisha; Cain, Kevin; Oeltmann, John E

    2015-12-01

    To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers. © 2015 John Wiley & Sons Ltd.

  19. A Multinomial Probit Model with Latent Factors

    DEFF Research Database (Denmark)

    Piatek, Rémi; Gensowski, Miriam

    2017-01-01

    be meaningfully linked to an economic model. We provide sufficient conditions that make this structure identified and interpretable. For inference, we design a Markov chain Monte Carlo sampler based on marginal data augmentation. A simulation exercise shows the good numerical performance of our sampler......We develop a parametrization of the multinomial probit model that yields greater insight into the underlying decision-making process, by decomposing the error terms of the utilities into latent factors and noise. The latent factors are identified without a measurement system, and they can...

  20. Reporting guidelines for diagnostic accuracy studies that use Bayesian latent class models (STARD-BLCM)

    DEFF Research Database (Denmark)

    Kostoulas, Polychronis; Nielsen, Søren S.; Branscum, Adam J.

    2017-01-01

    of disease status (i.e., disease status is a latent variable). Statistical methods were introduced in this context by Hui and Walter and have been succesfully applied since then, with the majority of the work being carried out in a Bayesian framework. While STARD provides useful reporting guidelines...... for studies designed to estimate the accuracy of tests when disease status is known. The original STARD statement was initially published in seven journals, while an updated version — STARD2015 — has been recently released. More than 200 biomedical journals encourage its use in their instructions to authors...

  1. Herpes simplex virus type 1 (HSV-1)-derived recombinant vectors for gene transfer and gene therapy.

    Science.gov (United States)

    Marconi, Peggy; Fraefel, Cornel; Epstein, Alberto L

    2015-01-01

    Herpes simplex virus type 1 (HSV-1 ) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153-kilobase pair (kbp) double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes the approach most commonly used to prepare recombinant HSV-1 vectors through homologous recombination, either in eukaryotic cells or in bacteria.

  2. Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

    Directory of Open Access Journals (Sweden)

    Samantha K Dunmire

    Full Text Available Epstein-Barr Virus (EBV causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza, respiratory syncytial virus (RSV, human rhinovirus (HRV, attenuated yellow fever virus (YFV, and Dengue fever virus (DENV, revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

  3. Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes

    Science.gov (United States)

    Dunmire, Samantha K.; Odumade, Oludare A.; Porter, Jean L.; Reyes-Genere, Juan; Schmeling, David O.; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C.; Balfour, Henry H.; Hogquist, Kristin A.

    2014-01-01

    Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans. PMID:24465555

  4. Competing risk model for reduction in life expectancy from radiogenic latent cancer

    International Nuclear Information System (INIS)

    Davis, H.T.

    1978-01-01

    Because of the large number of persons who could potentially receive low doses of radiation as a result of a nuclear reactor accident, the number of fatalities from latent cancers is generally larger than the early, or prompt, fatalities. For this reason the latent cancer fatality risk of reactor accidents is perceived as being more important than the early fatality risk. In addition, there exists the temptation to add the latent cancer fatality risk to the early fatality risk for the purpose of comparing reactor accident risks to other risks that society is exposed to, such as automobile accidents, airplane accidents, hurricanes, etc. However, the impact on the individual, and society as a whole, due to latent cancer fatalities is significantly different from the impact produced by early fatalities. Early fatalities generally result in appreciable life shortening for the affected individual while latent cancer fatalities generally result in very limited life shortening. A mathematical model was developed to express the reduction in life expectancy due to latent radiogenic cancer as a function of dose received

  5. Role of human immunodeficiency virus infection in the pathogenesis of human papillomavirus-associated cervical neoplasia.

    OpenAIRE

    Braun, L.

    1994-01-01

    Although many basic questions about the relationship between HIV and HPV infection remain unresolved, epidemiological studies have consistently shown a strong association between HIV infection and the development of HPV-related squamous intraepithelial neoplasia. This work indicates that HIV infection may promote the clinical manifestation of subclinical or latent HPV infection. Recent technical advances localizing virus DNA and gene products in situ will provide new avenues for investigation...

  6. The Big Bang of picorna-like virus evolution antedates the radiation of eukaryotic supergroups.

    Science.gov (United States)

    Koonin, Eugene V; Wolf, Yuri I; Nagasaki, Keizo; Dolja, Valerian V

    2008-12-01

    The recent discovery of RNA viruses in diverse unicellular eukaryotes and developments in evolutionary genomics have provided the means for addressing the origin of eukaryotic RNA viruses. The phylogenetic analyses of RNA polymerases and helicases presented in this Analysis article reveal close evolutionary relationships between RNA viruses infecting hosts from the Chromalveolate and Excavate supergroups and distinct families of picorna-like viruses of plants and animals. Thus, diversification of picorna-like viruses probably occurred in a 'Big Bang' concomitant with key events of eukaryogenesis. The origins of the conserved genes of picorna-like viruses are traced to likely ancestors including bacterial group II retroelements, the family of HtrA proteases and DNA bacteriophages.

  7. Avoiding and Correcting Bias in Score-Based Latent Variable Regression with Discrete Manifest Items

    Science.gov (United States)

    Lu, Irene R. R.; Thomas, D. Roland

    2008-01-01

    This article considers models involving a single structural equation with latent explanatory and/or latent dependent variables where discrete items are used to measure the latent variables. Our primary focus is the use of scores as proxies for the latent variables and carrying out ordinary least squares (OLS) regression on such scores to estimate…

  8. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Philana Ling Lin

    2016-07-01

    Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

  9. Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

    Science.gov (United States)

    Zhao, Xueli; Sun, Yipeng; Pu, Juan; Fan, Lihong; Shi, Weimin; Hu, Yanxin; Yang, Jun; Xu, Qi; Wang, Jingjing; Hou, Dongjun; Ma, Guangpeng; Liu, Jinhua

    2011-01-01

    Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

  10. Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

    Directory of Open Access Journals (Sweden)

    Xueli Zhao

    Full Text Available Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1 with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus. Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

  11. Skin Resistivity Value of Upper Trapezius Latent Trigger Points

    Directory of Open Access Journals (Sweden)

    Elżbieta Skorupska

    2015-01-01

    Full Text Available Introduction. The skin resistivity (SkR measurement is commonly recommended for acupoints measurement, but for trigger points (TrPs only one study is available. The purpose of the study was to evaluate SkR for latent TrPs compared to non-TrPs and the surrounding tissue. Material and Methods. Forty-two healthy volunteers with unilateral latent upper trapezius TrPs (12 men, 30 women aged 21–23 (mean age: 22.1 ± 0.6 y participated in the study. Keithley electrometer 610B was used for measuring SkR (Ag/AgCl self-adhesive, disposable ground electrode: 30 mm diameter. SkR was measured for latent TrPs and compared to opposite non-TrPs sites and the surrounding tissue. Results. The SkR decrease of TrPs-positive sites as compared to TrPs-negative sites and the surrounding tissue was confirmed. However, no statistically significant difference in the SkR value occurred when all data were analyzed. The same was confirmed after gender division and for TrPs-positive subjects examined for referred pain and twitch response presence. Conclusion. SkR reactive changes at latent TrPs are possible but the results were not consistent with the previous study. Thus, caution in applying SkR to latent TrPs isolation is recommended and its clinical use should not be encouraged yet. Further studies, especially on active TrPs, are yet required.

  12. Complete genome sequence of pronghorn virus, a pestivirus

    Science.gov (United States)

    The complete genome sequence of Pronghorn virus, a member of the Pestivirus genus of the Flaviviridae, was determined. The virus, originally isolated from a pronghorn antelope, had a genome of 12,287 nucleotides with a single open reading frame of 11,694 bases encoding 3898 amino acids....

  13. Latent variable modeling%建立隐性变量模型

    Institute of Scientific and Technical Information of China (English)

    蔡力

    2012-01-01

    @@ A latent variable model, as the name suggests,is a statistical model that contains latent, that is, unobserved, variables.Their roots go back to Spearman's 1904 seminal work[1] on factor analysis,which is arguably the first well-articulated latent variable model to be widely used in psychology, mental health research, and allied disciplines.Because of the association of factor analysis with early studies of human intelligence, the fact that key variables in a statistical model are, on occasion, unobserved has been a point of lingering contention and controversy.The reader is assured, however, that a latent variable,defined in the broadest manner, is no more mysterious than an error term in a normal theory linear regression model or a random effect in a mixed model.

  14. The origins of AIDS

    National Research Council Canada - National Science Library

    Pepin, Jacques

    2011-01-01

    ... urbanisation, prostitution and large-scale colonial medical campaigns intended to eradicate tropical diseases combined to disastrous effect to fuel the spread of the virus from its origins in Léopoldville to the rest of Africa, the Caribbean and ultimately worldwide. This is an essential new perspective on HIV/ AIDS and on the lessons that must be learned if we are to avoi...

  15. Accuracy of latent-variable estimation in Bayesian semi-supervised learning.

    Science.gov (United States)

    Yamazaki, Keisuke

    2015-09-01

    Hierarchical probabilistic models, such as Gaussian mixture models, are widely used for unsupervised learning tasks. These models consist of observable and latent variables, which represent the observable data and the underlying data-generation process, respectively. Unsupervised learning tasks, such as cluster analysis, are regarded as estimations of latent variables based on the observable ones. The estimation of latent variables in semi-supervised learning, where some labels are observed, will be more precise than that in unsupervised, and one of the concerns is to clarify the effect of the labeled data. However, there has not been sufficient theoretical analysis of the accuracy of the estimation of latent variables. In a previous study, a distribution-based error function was formulated, and its asymptotic form was calculated for unsupervised learning with generative models. It has been shown that, for the estimation of latent variables, the Bayes method is more accurate than the maximum-likelihood method. The present paper reveals the asymptotic forms of the error function in Bayesian semi-supervised learning for both discriminative and generative models. The results show that the generative model, which uses all of the given data, performs better when the model is well specified. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 31P-magnetic resonance spectroscopy: Impaired energy metabolism in latent hyperthyroidism

    International Nuclear Information System (INIS)

    Theissen, P.; Kaldewey, S.; Moka, D.; Bunke, J.; Voth, E.; Schicha, H.

    1993-01-01

    31 Phosphorous magnetic resonance spectroscopy allows an in vivo examination of energy metabolism. The present study was designed to evaluate whether in patients with latent hyperthyroidism alterations of muscle energy metabolism could be found similar to those observed in patients with overt hyperthyroidism. In 10 patients with overt hyperthyroidism before therapy and 20 with latent hyperthyroidism (also without therapy) and in 24 healthy volunteers magnetic resonance spectroscopy of the calf muscle was performed within a 1.5-Tesla magnet. Muscle concentrations of phosphocreatine, inorganic phosphate, and ATP were quantified compared to an external standard solution of K 2 HPO 4 . In the patients with overt hyperthyroidism and with latent hyperthyroidism a significant decrease of phosphocreatine was found. Further, the ATP concentration in patients with latent and manifest hyperthyroidism tended towards lower values. There were no significant differences in the decrease of phosphocreatine and ATP between both patient groups. Therefore, this study for the first time shows that alterations of energy metabolism in latent hyperthyroidism can be measured and that they are similar to those observed in overt hyperthyroidism. (orig.) [de

  17. [An overview on swine influenza viruses].

    Science.gov (United States)

    Yang, Shuai; Zhu, Wen-Fei; Shu, Yue-Long

    2013-05-01

    Swine influenza viruses (SIVs) are respiratory pathogens of pigs. They cause both economic bur den in livestock-dependent industries and serious global public health concerns in humans. Because of their dual susceptibility to human and avian influenza viruses, pigs are recognized as intermediate hosts for genetic reassortment and interspecies transmission. Subtypes H1N1, H1N2, and H3N2 circulate in swine populations around the world, with varied origin and genetic characteristics among different continents and regions. In this review, the role of pigs in evolution of influenza A viruses, the genetic evolution of SIVs and interspecies transmission of SIVs are described. Considering the possibility that pigs might produce novel influenza viruses causing more outbreaks and pandemics, routine epidemiological surveillance of influenza viruses in pig populations is highly recommended.

  18. Origin and evolution of dengue virus type 3 in Brazil.

    Science.gov (United States)

    de Araújo, Josélio Maria Galvão; Bello, Gonzalo; Romero, Hector; Nogueira, Rita Maria Ribeiro

    2012-01-01

    The incidence of dengue fever and dengue hemorrhagic fever in Brazil experienced a significant increase since the emergence of dengue virus type-3 (DENV-3) at the early 2000s. Despite the major public health concerns, there have been very few studies of the molecular epidemiology and time-scale of this DENV lineage in Brazil. In this study, we investigated the origin and dispersion dynamics of DENV-3 genotype III in Brazil by examining a large number (n=107) of E gene sequences sampled between 2001 and 2009 from diverse Brazilian regions. These Brazilian sequences were combined with 457 DENV-3 genotype III E gene sequences from 29 countries around the world. Our phylogenetic analysis reveals that there have been at least four introductions of the DENV-3 genotype III in Brazil, as signified by the presence of four phylogenetically distinct lineages. Three lineages (BR-I, BR-II, and BR-III) were probably imported from the Lesser Antilles (Caribbean), while the fourth one (BR-IV) was probably introduced from Colombia or Venezuela. While lineages BR-I and BR-II succeeded in getting established and disseminated in Brazil and other countries from the Southern Cone, lineages BR-III and BR-IV were only detected in one single individual each from the North region. The phylogeographic analysis indicates that DENV-3 lineages BR-I and BR-II were most likely introduced into Brazil through the Southeast and North regions around 1999 (95% HPD: 1998-2000) and 2001 (95% HPD: 2000-2002), respectively. These findings show that importation of DENV-3 lineages from the Caribbean islands into Brazil seems to be relatively frequent. Our study further suggests that the North and Southeast Brazilian regions were the most important hubs of introduction and spread of DENV-3 lineages and deserve an intense epidemiological surveillance.

  19. Origin and evolution of dengue virus type 3 in Brazil.

    Directory of Open Access Journals (Sweden)

    Josélio Maria Galvão de Araújo

    Full Text Available The incidence of dengue fever and dengue hemorrhagic fever in Brazil experienced a significant increase since the emergence of dengue virus type-3 (DENV-3 at the early 2000s. Despite the major public health concerns, there have been very few studies of the molecular epidemiology and time-scale of this DENV lineage in Brazil. In this study, we investigated the origin and dispersion dynamics of DENV-3 genotype III in Brazil by examining a large number (n=107 of E gene sequences sampled between 2001 and 2009 from diverse Brazilian regions. These Brazilian sequences were combined with 457 DENV-3 genotype III E gene sequences from 29 countries around the world. Our phylogenetic analysis reveals that there have been at least four introductions of the DENV-3 genotype III in Brazil, as signified by the presence of four phylogenetically distinct lineages. Three lineages (BR-I, BR-II, and BR-III were probably imported from the Lesser Antilles (Caribbean, while the fourth one (BR-IV was probably introduced from Colombia or Venezuela. While lineages BR-I and BR-II succeeded in getting established and disseminated in Brazil and other countries from the Southern Cone, lineages BR-III and BR-IV were only detected in one single individual each from the North region. The phylogeographic analysis indicates that DENV-3 lineages BR-I and BR-II were most likely introduced into Brazil through the Southeast and North regions around 1999 (95% HPD: 1998-2000 and 2001 (95% HPD: 2000-2002, respectively. These findings show that importation of DENV-3 lineages from the Caribbean islands into Brazil seems to be relatively frequent. Our study further suggests that the North and Southeast Brazilian regions were the most important hubs of introduction and spread of DENV-3 lineages and deserve an intense epidemiological surveillance.

  20. Epstein-Barr virus infection and gastric carcinoma in São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    L.F. Lopes

    2004-11-01

    Full Text Available Epstein-Barr virus (EBV is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32% gastric carcinomas, mostly from male patients (66.7%, with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3% were conventional adenocarcinomas, whereas four (66.7% were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea up to 18% (Germany. In Brazil, a previous work found EBV infection in 4 of 80 (5% gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. In the present study, the frequency of EBV-positive gastric carcinomas is similar to that reported in other series, and the clinicopathologic characteristics of these EBV-positive tumors are in agreement with the data in the literature.

  1. Latent class factor and cluster models, bi-plots and tri-plots and related graphical displays

    NARCIS (Netherlands)

    Magidson, J.; Vermunt, J.K.

    2001-01-01

    We propose an alternative method of conducting exploratory latent class analysis that utilizes latent class factor models, and compare it to the more traditional approach based on latent class cluster models. We show that when formulated in terms of R mutually independent, dichotomous latent

  2. Low-pathogenic influenza A viruses in North American diving ducks contribute to the emergence of a novel highly pathogenic influenza A(H7N8) virus

    Science.gov (United States)

    Xu, Yifei; Ramey, Andrew M.; Bowman, Andrew S; DeLiberto, Thomas J.; Killian, Mary Lea; Krauss, Scott; Nolting, Jacqueline M.; Torchetti, Mia Kim; Reeves, Andrew B.; Webby, Richard J.; Stallknecht, David E.; Wan, Xiu-Feng

    2017-01-01

    Introductions of low-pathogenic avian influenza (LPAI) viruses of subtypes H5 and H7 into poultry from wild birds have the potential to mutate to highly pathogenic avian influenza (HPAI) viruses, but such viruses' origins are often unclear. In January 2016, a novel H7N8 HPAI virus caused an outbreak in turkeys in Indiana, USA. To determine the virus's origin, we sequenced the genomes of 441 wild-bird origin influenza A viruses (IAVs) from North America and subjected them to evolutionary analyses. The results showed that the H7N8 LPAI virus most likely circulated among diving ducks in the Mississippi flyway during autumn 2015 and was subsequently introduced to Indiana turkeys, in which it evolved high pathogenicity. Preceding the outbreak, an isolate with six gene segments (PB2, PB1, PA, HA, NA, and NS) sharing >99% sequence identity with those of H7N8 turkey isolates was recovered from a diving duck sampled in Kentucky, USA. H4N8 IAVs from other diving ducks possessed five H7N8-like gene segments (PB2, PB1, NA, MP, and NS; >98% sequence identity). Our findings suggest that viral gene constellations circulating among diving ducks can contribute to the emergence of IAVs that affect poultry. Therefore, diving ducks may serve an important and understudied role in the maintenance, diversification, and transmission of IAVs in the wild-bird reservoir.

  3. Hit-and-run stimulation: a novel concept to reactivate latent HIV-1 infection without cytokine gene induction.

    Science.gov (United States)

    Wolschendorf, Frank; Duverger, Alexandra; Jones, Jennifer; Wagner, Frederic H; Huff, Jason; Benjamin, William H; Saag, Michael S; Niederweis, Michael; Kutsch, Olaf

    2010-09-01

    Current antiretroviral therapy (ART) efficiently controls HIV-1 replication but fails to eradicate the virus. Even after years of successful ART, HIV-1 can conceal itself in a latent state in long-lived CD4(+) memory T cells. From this latent reservoir, HIV-1 rebounds during treatment interruptions. Attempts to therapeutically eradicate this viral reservoir have yielded disappointing results. A major problem with previously utilized activating agents is that at the concentrations required for efficient HIV-1 reactivation, these stimuli trigger high-level cytokine gene expression (hypercytokinemia). Therapeutically relevant HIV-1-reactivating agents will have to trigger HIV-1 reactivation without the induction of cytokine expression. We present here a proof-of-principle study showing that this is a possibility. In a high-throughput screening effort, we identified an HIV-1-reactivating protein factor (HRF) secreted by the nonpathogenic bacterium Massilia timonae. In primary T cells and T-cell lines, HRF triggered a high but nonsustained peak of nuclear factor kappa B (NF-kappaB) activity. While this short NF-kappaB peak potently reactivated latent HIV-1 infection, it failed to induce gene expression of several proinflammatory NF-kappaB-dependent cellular genes, such as those for tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and gamma interferon (IFN-gamma). Dissociation of cellular and viral gene induction was achievable, as minimum amounts of Tat protein, synthesized following application of a short NF-kappaB pulse, triggered HIV-1 transactivation and subsequent self-perpetuated HIV-1 expression. In the absence of such a positive feedback mechanism, cellular gene expression was not sustained, suggesting that strategies modulating the NF-kappaB activity profile could be used to selectively trigger HIV-1 reactivation.

  4. Origins and challenges of viral dark matter.

    Science.gov (United States)

    Krishnamurthy, Siddharth R; Wang, David

    2017-07-15

    The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A novel single-stranded RNA virus isolated from a phytopathogenic filamentous fungus, Rosellinia necatrix, with similarity to hypo-like viruses

    Directory of Open Access Journals (Sweden)

    Rui eZhang

    2014-07-01

    Full Text Available Here we report a biological and molecular characterization of a novel positive-sense RNA virus isolated from a field isolate (NW10 of a filamentous phytopathogenic fungus, the white root rot fungus that is designated as Rosellinia necatrix fusarivirus 1 (RnFV1. A recently developed technology using zinc ions allowed us to transfer RnFV1 to two mycelially incompatible Rosellinia necatrix strains. A biological comparison of the virus-free and -recipient isogenic fungal strains suggested that RnFV1 infects latently and thus has no potential as a virocontrol agent. The virus has an undivided positive-sense RNA genome of 6286 nucleotides excluding a poly (A tail. The genome possesses two non-overlapping open reading frames (ORFs: a large ORF1 that encodes polypeptides with RNA replication functions and a smaller ORF2 that encodes polypeptides of unknown function. A lack of coat protein genes was suggested by the failure of virus particles from infected mycelia. No evidence was obtained by Northern analysis or classical 5'-RACE for the presence of subgenomic RNA for the downstream ORF. Sequence similarities were found in amino-acid sequence between RnFV1 putative proteins and counterparts of a previously reported mycovirus, Fusarium graminearum virus 1 (FgV1. Interestingly, several related sequences were detected by BLAST searches of independent transcriptome assembly databases one of which probably represents an entire virus genome. Phylogenetic analysis based on the conserved RNA-dependent RNA polymerase showed that RnFV1, FgV1, and these similar sequences are grouped in a cluster distinct from distantly related hypoviruses. It is proposed that a new taxonomic family termed Fusariviridae be created to include RnFV1and FgV1.

  6. Avian influenza A viruses: From zoonosis to pandemic

    NARCIS (Netherlands)

    M. Richard (Mathilde); M.T. de Graaf (Marieke); S. Herfst (Sander)

    2014-01-01

    textabstractZoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in

  7. Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

    Science.gov (United States)

    Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

    2017-12-05

    Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

  8. A solar air collector with integrated latent heat thermal storage

    Directory of Open Access Journals (Sweden)

    Klimes Lubomir

    2012-04-01

    Full Text Available Simulations of the behaviour of a solar air collector with integrated latent heat thermal storage were performed. The model of the collector was created with the use of coupling between TRNSYS 17 and MATLAB. Latent heat storage (Phase Change Material - PCM was integrated with the solar absorber. The model of the latent heat storage absorber was created in MATLAB and the model of the solar air collector itself was created in TRNSYS with the use of TYPE 56. The model of the latent heat storage absorber allows specification of the PCM properties as well as other parameters. The simulated air collector was the front and back pass collector with the absorber in the middle of the air cavity. Two variants were considered for comparison; the light-weight absorber made of sheet metal and the heat-storage absorber with the PCM. Simulations were performed for the climatic conditions of the Czech Republic (using TMY weather data.

  9. STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

    Science.gov (United States)

    Atkins, Elisha; Huang, Wei Cheng

    1958-01-01

    A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses. PMID:13513908

  10. Infection of goose with genotype VIId Newcastle disease virus of goose origin elicits strong immune responses at early stage

    Directory of Open Access Journals (Sweden)

    Qianqian Xu

    2016-10-01

    Full Text Available Newcastle disease (ND, caused by virulent strains of Newcastle disease virus (NDV, is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06. The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR1–3, 5, 7 and 15, avian β-defensin (AvBD 5–7, 10, 12 and 16, cytokines interleukin (IL-8, IL-18, IL-1β and interferon-γ, inducible NO synthase (iNOS, and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10 and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

  11. Chest Radiographic Findings of Novel Swine-Origin Influenza A (H1N1) Virus Infection in Children

    Energy Technology Data Exchange (ETDEWEB)

    Bae, So Young; Hong, Eun Sook; Paik, Sang Hyun; Park, Seong Jin; Cha, Jang Gyu; Lee, Hae Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Jang, Yun Woo [Dept. of Radiology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2011-06-15

    To analyze chest radiographic findings in children infected with laboratory confirmed novel swine-origin influenza A (H1N1) virus. Three hundred seventy-two out of 2,014 children with laboratory confirmed H1N1 infection and who also underwent a chest radiograph from September to November 2009 were enrolled in this study. Patients were divided into in-patients, out-patients, and patients with co-infections and further subdivided into with underlying disease and without underlying disease as well as age (<2 years old, 2-5 years, 5-10 years, 10-18 years old). The initial radiographs were evaluated for radiographic findings and the anatomic distribution of abnormalities. The initial radiographs were abnormal in 154 (41.39%) patients. The predominant radiographic findings were peribronchial wall opacity found in 85 (22.84%) patients and hyperinflation observed in 69 (18.54%) patients. Further, 75 (71.42%) patients exhibited central predominance and the right lower lung zone was also commonly involved. There were statistically significant differences in the radiological findings between in-patient and out-patient groups. However, there were no significant differences in the radiographic findings between in-patients and the co-infection group with respect the presence of underlying disease and age. Initial radiographs of children with laboratory confirmed H1N1 virus were abnormal in 41.39% of cases. The common radiographic findings included peribronchial opacities, hyperinflation, lower lung zonal distribution, and central predominance

  12. Latent class models for classification

    NARCIS (Netherlands)

    Vermunt, J.K.; Magidson, J.

    2003-01-01

    An overview is provided of recent developments in the use of latent class (LC) and other types of finite mixture models for classification purposes. Several extensions of existing models are presented. Two basic types of LC models for classification are defined: supervised and unsupervised

  13. Epstein-Barr Virus BKRF4 Gene Product Is Required for Efficient Progeny Production.

    Science.gov (United States)

    Masud, H M Abdullah Al; Watanabe, Takahiro; Yoshida, Masahiro; Sato, Yoshitaka; Goshima, Fumi; Kimura, Hiroshi; Murata, Takayuki

    2017-12-01

    Epstein-Barr virus (EBV), a member of human gammaherpesvirus, infects mainly B cells. EBV has two alternative life cycles, latent and lytic, and is reactivated occasionally from the latent stage to the lytic cycle. To combat EBV-associated disorders, understanding the molecular mechanisms of the EBV lytic replication cycle is also important. Here, we focused on an EBV lytic gene, BKRF4. Using our anti-BKRF4 antibody, we revealed that the BKRF4 gene product is expressed during the lytic cycle with late kinetics. To characterize the role of BKRF4, we constructed BKRF4-knockout mutants using the bacterial artificial chromosome (BAC) and CRISPR/Cas9 systems. Although disruption of the BKRF4 gene had almost no effect on viral protein expression and DNA synthesis, it significantly decreased progeny virion levels in HEK293 and Akata cells. Furthermore, we show that BKRF4 is involved not only in production of progeny virions but also in increasing the infectivity of the virus particles. Immunoprecipitation assays revealed that BKRF4 interacted with a virion protein, BGLF2. We showed that the C-terminal region of BKRF4 was critical for this interaction and for efficient progeny production. Immunofluorescence analysis revealed that BKRF4 partially colocalized with BGLF2 in the nucleus and perinuclear region. Finally, we showed that BKRF4 is a phosphorylated, possible tegument protein and that the EBV protein kinase BGLF4 may be important for this phosphorylation. Taken together, our data suggest that BKRF4 is involved in the production of infectious virions. IMPORTANCE Although the latent genes of EBV have been studied extensively, the lytic genes are less well characterized. This study focused on one such lytic gene, BKRF4, which is conserved only among gammaherpesviruses (ORF45 of Kaposi's sarcoma-associated herpesvirus or murine herpesvirus 68). After preparing the BKRF4 knockout virus using B95-8 EBV-BAC, we demonstrated that the BKRF4 gene was involved in infectious

  14. On Latent Growth Models for Composites and Their Constituents.

    Science.gov (United States)

    Hancock, Gregory R; Mao, Xiulin; Kher, Hemant

    2013-09-01

    Over the last decade and a half, latent growth modeling has become an extremely popular and versatile technique for evaluating longitudinal change and its determinants. Most common among the models applied are those for a single measured variable over time. This model has been extended in a variety of ways, most relevant for the current work being the multidomain and the second-order latent growth models. Whereas the former allows for growth function characteristics to be modeled for multiple outcomes simultaneously, with the degree of growth characteristics' relations assessed within the model (e.g., cross-domain slope factor correlations), the latter models growth in latent outcomes, each of which has effect indicators repeated over time. But what if one has an outcome that is believed to be formative relative to its indicator variables rather than latent? In this case, where the outcome is a composite of multiple constituents, modeling change over time is less straightforward. This article provides analytical and applied details for simultaneously modeling growth in composites and their constituent elements, including a real data example using a general computer self-efficacy questionnaire.

  15. Piecewise Linear-Linear Latent Growth Mixture Models with Unknown Knots

    Science.gov (United States)

    Kohli, Nidhi; Harring, Jeffrey R.; Hancock, Gregory R.

    2013-01-01

    Latent growth curve models with piecewise functions are flexible and useful analytic models for investigating individual behaviors that exhibit distinct phases of development in observed variables. As an extension of this framework, this study considers a piecewise linear-linear latent growth mixture model (LGMM) for describing segmented change of…

  16. Rapid detection of drug metabolites in latent fingermarks.

    Science.gov (United States)

    Hazarika, Pompi; Jickells, Sue M; Russell, David A

    2009-01-01

    Magnetic particles functionalised with anti-cotinine antibody have been used to image latent fingermarks through the detection of the cotinine antigen in the sweat deposited within the fingerprints of smokers. The antibody-magnetic particle conjugates are readily applied to latent fingerprints while excess reagents are removed through the use of a magnetic wand. The results have shown that drug metabolites, such as cotinine, can be detected and used to image the fingermark to establish the identity of an individual within 15 minutes.

  17. Chayote mosaic virus, a New Tymovirus Infecting Cucurbitaceae.

    Science.gov (United States)

    Bernal, J J; Jiménez, I; Moreno, M; Hord, M; Rivera, C; Koenig, R; Rodríguez-Cerezo, E

    2000-10-01

    ABSTRACT Chayote mosaic virus (ChMV) is a putative tymovirus isolated from chayote crops in Costa Rica. ChMV was characterized at the host range, serological, and molecular levels. ChMV was transmitted mechanically and induced disease symptoms mainly in Cucurbitaceae hosts. Asymptomatic infections were detected in other host families. Serologically, ChMV is related to the Andean potato latent virus (APLV) and the Eggplant mosaic virus (EMV), both members of the genus Tymovirus infecting solanaceous hosts in the Caribbean Basin and South America. The sequence of the genomic RNA of ChMV was determined and its genetic organization was typical of tymoviruses. Comparisons with other tymoviral sequences showed that ChMV was a new member of the genus Tymovirus. The phylogenetic analyses of the coat protein gene were consistent with serological comparisons and positioned ChMV within a cluster of tymoviruses infecting mainly cucurbit or solanaceous hosts, including APLV and EMV. Phylogenetic analyses of the replicase protein gene confirmed the close relationship of ChMV and EMV. Our results suggest that ChMV is related to two tymoviruses (APLV and EMV) of proximal geographical provenance but with different natural host ranges. ChMV is the first cucurbit-infecting tymovirus to be fully characterized at the genomic level.

  18. Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

    Science.gov (United States)

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

  19. Different evolutionary trends of swine H1N2 influenza viruses in Italy compared to European viruses.

    Science.gov (United States)

    Moreno, Ana; Gabanelli, Elena; Sozzi, Enrica; Lelli, Davide; Chiapponi, Chiara; Ciccozzi, Massimo; Zehender, Gianguglielmo; Cordioli, Paolo

    2013-12-01

    European H1N2 swine influenza viruses (EU H1N2SIVs) arose from multiple reassortment events among human H1N1, human H3N2, and avian influenza viruses. We investigated the evolutionary dynamics of 53 Italian H1N2 strains by comparing them with EU H1N2 SIVs. Hemagglutinin (HA) phylogeny revealed Italian strains fell into four groups: Group A and B (41 strains) had a human H1 similar to EU H1N2SIVs, which probably originated in 1986. However Group B (38 strains) formed a subgroup that had a two-amino acid deletion at positions 146/147 in HA. Group C (11 strains) contained an avian H1 that probably originated in 1996, and Group D (1 strain) had an H1 characteristic of the 2009 pandemic strain. Neuraminidase (NA) phylogeny suggested a series of genomic reassortments had occurred. Group A had an N2 that originated from human H3N2 in the late 1970s. Group B had different human N2 that most likely arose from a reassortment with the more recent human H3N2 virus, which probably occurred in 2000. Group C had an avian-like H1 combined with an N2 gene from one of EU H1N2SIVs, EU H3N2SIVs or Human H3N2. Group D was part of the EU H3N2SIVs clade. Although selection pressure for HA and NA was low, several positively selected sites were identified in both proteins, some of which were antigenic, suggesting selection influenced the evolution of SIV. The data highlight different evolutionary trends between European viruses and currently circulating Italian B strains and show the establishment of reassortant strains involving human viruses in Italian pigs.

  20. Viruses in the Oceanic Basement.

    Science.gov (United States)

    Nigro, Olivia D; Jungbluth, Sean P; Lin, Huei-Ting; Hsieh, Chih-Chiang; Miranda, Jaclyn A; Schvarcz, Christopher R; Rappé, Michael S; Steward, Grieg F

    2017-03-07

    Microbial life has been detected well into the igneous crust of the seafloor (i.e., the oceanic basement), but there have been no reports confirming the presence of viruses in this habitat. To detect and characterize an ocean basement virome, geothermally heated fluid samples (ca. 60 to 65°C) were collected from 117 to 292 m deep into the ocean basement using seafloor observatories installed in two boreholes (Integrated Ocean Drilling Program [IODP] U1362A and U1362B) drilled in the eastern sediment-covered flank of the Juan de Fuca Ridge. Concentrations of virus-like particles in the fluid samples were on the order of 0.2 × 10 5 to 2 × 10 5  ml -1 ( n = 8), higher than prokaryote-like cells in the same samples by a factor of 9 on average (range, 1.5 to 27). Electron microscopy revealed diverse viral morphotypes similar to those of viruses known to infect bacteria and thermophilic archaea. An analysis of virus-like sequences in basement microbial metagenomes suggests that those from archaeon-infecting viruses were the most common (63 to 80%). Complete genomes of a putative archaeon-infecting virus and a prophage within an archaeal scaffold were identified among the assembled sequences, and sequence analysis suggests that they represent lineages divergent from known thermophilic viruses. Of the clustered regularly interspaced short palindromic repeat (CRISPR)-containing scaffolds in the metagenomes for which a taxonomy could be inferred (163 out of 737), 51 to 55% appeared to be archaeal and 45 to 49% appeared to be bacterial. These results imply that the warmed, highly altered fluids in deeply buried ocean basement harbor a distinct assemblage of novel viruses, including many that infect archaea, and that these viruses are active participants in the ecology of the basement microbiome. IMPORTANCE The hydrothermally active ocean basement is voluminous and likely provided conditions critical to the origins of life, but the microbiology of this vast habitat is not

  1. Latent effectiveness of desiccant wheel: A silica gels- water system

    International Nuclear Information System (INIS)

    Rabah, A. A.; Mohamed, S. A.

    2009-01-01

    A latent heat effectiveness model in term of dimensionless groups? =f (NTU, m * ,Crm * ) for energy wheel has been analytically derived. The energy wheel is divided into humidification and dehumidification sections. For each section macroscopic mass differential equations for gas and the matrix were applied. In this process local latent effectiveness (? c ,? h ) for the humidification and dehumidification section of the wheel were obtained. The Latent effectiveness of the wheel is then derived form local effectiveness [? =f (? c ,? h)]. The model is compared with the existing experimental investigation and manufacturer data for energy wheel. More than 90% of the experimental data within a confidence limit of 95%. (Author)

  2. Intercept Centering and Time Coding in Latent Difference Score Models

    Science.gov (United States)

    Grimm, Kevin J.

    2012-01-01

    Latent difference score (LDS) models combine benefits derived from autoregressive and latent growth curve models allowing for time-dependent influences and systematic change. The specification and descriptions of LDS models include an initial level of ability or trait plus an accumulation of changes. A limitation of this specification is that the…

  3. Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution

    Directory of Open Access Journals (Sweden)

    Kishima Yuji

    2004-10-01

    Full Text Available Abstract Background Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV-like sequences (ERTBVs have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response. Results We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome. Conclusions These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease.

  4. Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

    Science.gov (United States)

    Weller, Sandra K.; Sawitzke, James A.

    2015-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

  5. Investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza A(H10N8) in Nanchang City, China.

    Science.gov (United States)

    Ni, Xiansheng; He, Fenglan; Hu, Maohong; Zhou, Xianfeng; Wang, Bin; Feng, Changhua; Wu, Yumei; Li, Youxing; Tu, Junling; Li, Hui; Liu, Mingbin; Chen, Haiying; Chen, Shengen

    2015-01-01

    Multiple reassortment events within poultry and wild birds had resulted in the establishment of another novel avian influenza A(H10N8) virus, and finally resulted in human death in Nanchang, China. However, there was a paucity of information on the prevalence of avian influenza virus in poultry and wild birds in Nanchang area. We investigated avian influenza virus in poultry and wild birds from live poultry markets, poultry countyards, delivery vehicles, and wild-bird habitats in Nanchang. We analyzed 1036 samples from wild birds and domestic poultry collected from December 2013 to February 2014. Original biological samples were tested for the presence of avian influenza virus using specific primer and probe sets of H5, H7, H9, H10 and N8 subtypes by real-time RT-PCR. In our analysis, the majority (97.98%) of positive samples were from live poultry markets. Among the poultry samples from chickens and ducks, AIV prevalence was 26.05 and 30.81%, respectively. Mixed infection of different HA subtypes was very common. Additionally, H10 subtypes coexistence with N8 was the most prevalent agent during the emergence of H10N8. This event illustrated a long-term surveillance was so helpful for pandemic preparedness and response. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

    Science.gov (United States)

    Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

    2017-06-01

    A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

  7. Large-scale weakly supervised object localization via latent category learning.

    Science.gov (United States)

    Chong Wang; Kaiqi Huang; Weiqiang Ren; Junge Zhang; Maybank, Steve

    2015-04-01

    Localizing objects in cluttered backgrounds is challenging under large-scale weakly supervised conditions. Due to the cluttered image condition, objects usually have large ambiguity with backgrounds. Besides, there is also a lack of effective algorithm for large-scale weakly supervised localization in cluttered backgrounds. However, backgrounds contain useful latent information, e.g., the sky in the aeroplane class. If this latent information can be learned, object-background ambiguity can be largely reduced and background can be suppressed effectively. In this paper, we propose the latent category learning (LCL) in large-scale cluttered conditions. LCL is an unsupervised learning method which requires only image-level class labels. First, we use the latent semantic analysis with semantic object representation to learn the latent categories, which represent objects, object parts or backgrounds. Second, to determine which category contains the target object, we propose a category selection strategy by evaluating each category's discrimination. Finally, we propose the online LCL for use in large-scale conditions. Evaluation on the challenging PASCAL Visual Object Class (VOC) 2007 and the large-scale imagenet large-scale visual recognition challenge 2013 detection data sets shows that the method can improve the annotation precision by 10% over previous methods. More importantly, we achieve the detection precision which outperforms previous results by a large margin and can be competitive to the supervised deformable part model 5.0 baseline on both data sets.

  8. Reliability measures in item response theory: manifest versus latent correlation functions.

    Science.gov (United States)

    Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Verbeke, Geert; De Boeck, Paul

    2015-02-01

    For item response theory (IRT) models, which belong to the class of generalized linear or non-linear mixed models, reliability at the scale of observed scores (i.e., manifest correlation) is more difficult to calculate than latent correlation based reliability, but usually of greater scientific interest. This is not least because it cannot be calculated explicitly when the logit link is used in conjunction with normal random effects. As such, approximations such as Fisher's information coefficient, Cronbach's α, or the latent correlation are calculated, allegedly because it is easy to do so. Cronbach's α has well-known and serious drawbacks, Fisher's information is not meaningful under certain circumstances, and there is an important but often overlooked difference between latent and manifest correlations. Here, manifest correlation refers to correlation between observed scores, while latent correlation refers to correlation between scores at the latent (e.g., logit or probit) scale. Thus, using one in place of the other can lead to erroneous conclusions. Taylor series based reliability measures, which are based on manifest correlation functions, are derived and a careful comparison of reliability measures based on latent correlations, Fisher's information, and exact reliability is carried out. The latent correlations are virtually always considerably higher than their manifest counterparts, Fisher's information measure shows no coherent behaviour (it is even negative in some cases), while the newly introduced Taylor series based approximations reflect the exact reliability very closely. Comparisons among the various types of correlations, for various IRT models, are made using algebraic expressions, Monte Carlo simulations, and data analysis. Given the light computational burden and the performance of Taylor series based reliability measures, their use is recommended. © 2014 The British Psychological Society.

  9. Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1

    Directory of Open Access Journals (Sweden)

    Wang Pu

    2010-10-01

    Full Text Available Abstract The Epstein-Barr Virus (EBV Nuclear Antigen 1 (EBNA1 protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP, regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP combined with massively parallel deep-sequencing (ChIP-Seq was used to identify cellular sites bound by EBNA1. Sites identified by ChIP-Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A consensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, suggesting that some of these sites are indirectly bound by EBNA1. EBNA1 also bound close to the transcriptional start sites of a large number of cellular genes, including HDAC3, CDC7, and MAP3K1, which we show are positively regulated by EBNA1. EBNA1 binding sites were enriched in some repetitive elements, especially LINE 1 retrotransposons, and had weak correlations with histone modifications and ORC binding. We conclude that EBNA1 can interact with a large number of cellular genes and chromosomal loci in latently infected cells, but that these sites are likely to represent a complex ensemble of direct and indirect EBNA

  10. FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

    Directory of Open Access Journals (Sweden)

    Murphy Brian

    2012-02-01

    Full Text Available Abstract Background Feline immunodeficiency virus (FIV is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. Results In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Conclusions Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.

  11. Longitudinal Physical Activity Patterns Among Older Adults: A Latent Transition Analysis.

    Science.gov (United States)

    Mooney, Stephen J; Joshi, Spruha; Cerdá, Magdalena; Kennedy, Gary J; Beard, John R; Rundle, Andrew G

    2018-05-14

    Most epidemiologic studies of physical activity measure either total energy expenditure or engagement in a single activity type, such as walking. These approaches may gloss over important nuances in activity patterns. We performed a latent transition analysis to identify patterns of activity types as well as neighborhood and individual determinants of changes in those activity patterns over two years in a cohort of 2,023 older adult residents of New York City, NY, surveyed between 2011 and 2013. We identified seven latent classes: 1) Mostly Inactive, 2) Walking, 3) Exercise, 4) Household Activities and Walking, 5) Household Activities and Exercise, 6) Gardening and Household Activities, and 7) Gardening, Household Activities, and Exercise. The majority of subjects retained the same activity patterns between waves (54% unchanged between waves 1 and 2, 66% unchanged between waves 2 and 3).Most latent class transitions were between classes distinguished only by one form of activity, and only neighborhood unemployment was consistently associated with changing between activity latent classes. Future latent transition analyses of physical activity would benefit from larger cohorts and longer follow-up periods to assess predictors of and long-term impacts of changes in activity patterns.

  12. Latent factors and route choice behaviour

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo

    . A reliable dataset was prepared through measures of internal consistency and sampling adequacy, and data were analyzed with a proper application of factor analysis to the route choice context. For the dataset obtained from the survey, six latent constructs affecting driver behaviour were extracted and scores...... on each factor for each survey participant were calculated. Path generation algorithms were examined with respect to observed behaviour, through a measure of reproduction with deterministic techniques of the routes indicated in the answers to the survey. Results presented evidence that the majority...... and Link Nested Logit. Estimates were produced from model specifications that considered level-of-service, label and facility dummy variables. Moreover, a modelling framework was designed to represent drivers’ choices as affected by the latent constructs extracted with factor analysis. Previous experience...

  13. Studies on the pathogenesis of fever with influenzal viruses. I. The appearance of an endogenous pyrogen in the blood following intravenous injection of virus.

    Science.gov (United States)

    ATKINS, E; HUANG, W C

    1958-03-01

    A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN(2) failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.

  14. Avian influenza virus (H5N1): a threat to human health

    NARCIS (Netherlands)

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes.

  15. Influenza virus and endothelial cells: A species specific relationship

    NARCIS (Netherlands)

    K.R. Short (Kirsty); E.J.B. Veldhuis Kroeze (Edwin); L.A. Reperant (Leslie); M. Richard (Mathilde); T. Kuiken (Thijs)

    2014-01-01

    textabstractInfluenza A virus (IAV) infection is an important cause of respiratory disease in humans. The original reservoirs of IAV are wild waterfowl and shorebirds, where virus infection causes limited, if any, disease. Both in humans and in wild waterbirds, epithelial cells are the main target

  16. Rapid visualization of latent fingermarks using gold seed-mediated enhancement

    Directory of Open Access Journals (Sweden)

    Chia-Hao Su

    2016-11-01

    Full Text Available Abstract Background Fingermarks are one of the most important and useful forms of physical evidence in forensic investigations. However, latent fingermarks are not directly visible, but can be visualized due to the presence of other residues (such as inorganic salts, proteins, polypeptides, enzymes and human metabolites which can be detected or recognized through various strategies. Convenient and rapid techniques are still needed to provide obvious contrast between the background and the fingermark ridges and to then visualize latent fingermark with a high degree of selectivity and sensitivity. Results In this work, lysozyme-binding aptamer-conjugated Au nanoparticles (NPs are used to recognize and target lysozyme in the fingermark ridges, and Au+-complex solution is used as a growth agent to reduce Au+ from Au+ to Au0 on the surface of the Au NPs. Distinct fingermark patterns were visualized on a range of professional forensic within 3 min; the resulting images could be observed by the naked eye without background interference. The entire processes from fingermark collection to visualization only entails two steps and can be completed in less than 10 min. The proposed method provides cost and time savings over current fingermark visualization methods. Conclusions We report a simple, inexpensive, and fast method for the rapid visualization of latent fingermarks on the non-porous substrates using Au seed-mediated enhancement. Au seed-mediated enhancement is used to achieve the rapid visualization of latent fingermarks on non-porous substrates by the naked eye without the use of expensive or sophisticated instruments. The proposed approach offers faster detection and visualization of latent fingermarks than existing methods. The proposed method is expected to increase detection efficiency for latent fingermarks and reduce time requirements and costs for forensic investigations.

  17. Gene Variants Associated with Antisocial Behaviour: A Latent Variable Approach

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V.; Lee, Maria; Yrigollen, Carolyn M.; Pakstis, Andrew J.; Katsovich, Liliya; Olds, David L.; Grigorenko, Elena L.; Leckman, James F.

    2013-01-01

    Objective: The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods: Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a…

  18. Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.

    Directory of Open Access Journals (Sweden)

    Franziska Dağ

    2014-02-01

    Full Text Available Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blocks mouse CMV replication at the level of IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN-mediated inhibition of IE genes was entirely reversible, arguing that the IFN-effect may be consistent with viral latency. Importantly, the response to IFNβ is stochastic, and MCMV IE transcription and replication were repressed only in IFN-responsive cells, while the IFN-unresponsive cells remained permissive for lytic MCMV infection. IFN blocked the viral lytic replication cycle by upregulating the nuclear domain 10 (ND10 components, PML, Sp100 and Daxx, and their knockdown by shRNA rescued viral replication in the presence of IFNβ. Finally, IFNβ prevented MCMV reactivation from endothelial cells derived from latently infected mice, validating our results in a biologically relevant setting. Therefore, our data do not only define for the first time the molecular mechanism of IFN-mediated control of CMV infection, but also indicate that the reversible inhibition of the virus lytic cycle by IFNβ is consistent with the establishment of CMV latency.

  19. Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: A latent-class analysis.

    Directory of Open Access Journals (Sweden)

    Tan N Doan

    Full Text Available Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST and interferon-gamma release assays (IGRAs for LTBI diagnosis in various patient populations using Bayesian latent class modelling.Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85% and 52% (50-53%, respectively. The specificity of QFT-GIT was 97% (96-97% in non-BCG-vaccinated and 93% (92-94% in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100% and 79% (76-82%, respectively. T-SPOT.TB has comparable specificity (97% for both tests and better sensitivity (68% versus 52% than QFT-GIT in immune-competent adults

  20. Epstein-Barr Virus MicroRNA miR-BART20-5p Suppresses Lytic Induction by Inhibiting BAD-Mediated caspase-3-Dependent Apoptosis.

    Science.gov (United States)

    Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

    2016-02-01

    Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with a variety of tumor types. EBV can establish latency or undergo lytic replication in host cells. In general, EBV remains latent in tumors and expresses a limited repertoire of latent proteins to avoid host immune surveillance. When the lytic cycle is triggered by some as-yet-unknown form of stimulation, lytic gene expression and progeny virus production commence. Thus far, the exact mechanism of EBV latency maintenance and the in vivo triggering signal for lytic induction have yet to be elucidated. Previously, we have shown that the EBV microRNA miR-BART20-5p directly targets the immediate early genes BRLF1 and BZLF1 as well as Bcl-2-associated death promoter (BAD) in EBV-associated gastric carcinoma. In this study, we found that both mRNA and protein levels of BRLF1 and BZLF1 were suppressed in cells following BAD knockdown and increased after BAD overexpression. Progeny virus production was also downregulated by specific knockdown of BAD. Our results demonstrated that caspase-3-dependent apoptosis is a prerequisite for BAD-mediated EBV lytic cycle induction. Therefore, our data suggest that miR-BART20-5p plays an important role in latency maintenance and tumor persistence of EBV-associated gastric carcinoma by inhibiting BAD-mediated caspase-3-dependent apoptosis, which would trigger immediate early gene expression. EBV has an ability to remain latent in host cells, including EBV-associated tumor cells hiding from immune surveillance. However, the exact molecular mechanisms of EBV latency maintenance remain poorly understood. Here, we demonstrated that miR-BART20-5p inhibited the expression of EBV immediate early genes indirectly, by suppressing BAD-induced caspase-3-dependent apoptosis, in addition to directly, as we previously reported. Our study suggests that EBV-associated tumor cells might endure apoptotic stress to some extent and remain latent with the aid of miR-BART20-5p. Blocking the

  1. Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

    Science.gov (United States)

    Mehta, Satish; Pierson, Duane L.

    2010-01-01

    Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

  2. Latent Toxoplasma gondii infection leads to improved action control.

    Science.gov (United States)

    Stock, Ann-Kathrin; Heintschel von Heinegg, Evelyn; Köhling, Hedda-Luise; Beste, Christian

    2014-03-01

    The parasite Toxoplasma gondii has been found to manipulate the behavior of its secondary hosts to increase its own dissemination which is commonly believed to be to the detriment of the host (manipulation hypothesis). The manipulation correlates with an up-regulation of dopaminergic neurotransmission. In humans, different pathologies have been associated with T. gondii infections but most latently infected humans do not seem to display overt impairments. Since a dopamine plus does not necessarily bear exclusively negative consequences in humans, we investigated potential positive consequences of latent toxoplasmosis (and the presumed boosting of dopaminergic neurotransmission) on human cognition and behavior. For this purpose, we focused on action cascading which has been shown to be modulated by dopamine. Based on behavioral and neurophysiological (EEG) data obtained by means of a stop-change paradigm, we were able to demonstrate that healthy young humans can actually benefit from latent T. gondii infection as regards their performance in this task (as indicated by faster response times and a smaller P3 component). The data shows that a latent infection which is assumed to affect the dopaminergic system can lead to paradoxical improvements of cognitive control processes in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

    Science.gov (United States)

    Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

    2017-05-01

    Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors

  4. A Review of the Latent and Manifest Benefits (LAMB) Scale

    Science.gov (United States)

    Muller, Juanita; Waters, Lea

    2012-01-01

    The latent and manifest benefits (LAMB) scale (Muller, Creed, Waters & Machin, 2005) was designed to measure the latent and manifest benefits of employment and provide a single scale to test Jahoda's (1981) and Fryer's (1986) theories of unemployment. Since its publication in 2005 there have been 13 studies that have used the scale with 5692…

  5. The Ozobranchus leech is a candidate mechanical vector for the fibropapilloma-associated turtle herpesvirus found latently infecting skin tumors on Hawaiian green turtles (Chelonia mydas)

    International Nuclear Information System (INIS)

    Greenblatt, Rebecca J.; Work, Thierry M.; Balazs, George H.; Sutton, Claudia A.; Casey, Rufina N.; Casey, James W.

    2004-01-01

    Fibropapillomatosis (FP) of marine turtles is a neoplastic disease of ecological concern. A fibropapilloma-associated turtle herpesvirus (FPTHV) is consistently present, usually at loads exceeding one virus copy per tumor cell. DNA from an array of parasites of green turtles (Chelonia mydas) was examined with quantitative PCR (qPCR) to determine whether any carried viral loads are sufficient to implicate them as vectors for FPTHV. Marine leeches (Ozobranchus spp.) were found to carry high viral DNA loads; some samples approached 10 million copies per leech. Isopycnic sucrose density gradient/qPCR analysis confirmed that some of these copies were associated with particles of the density of enveloped viruses. The data implicate the marine leech Ozobranchus as a mechanical vector for FPTHV. Quantitative RT-PCR analysis of FPTHV gene expression indicated that most of the FPTHV copies in a fibropapilloma have restricted DNA polymerase expression, suggestive of latent infection

  6. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma

    DEFF Research Database (Denmark)

    Anderton, J A; Bose, S; Vockerodt, M

    2011-01-01

    ), an Epstein-Barr virus (EBV) associated malignancy. KDM6B is over-expressed in primary HL and induced by the EBV oncogene, latent membrane protein (LMP1) in GC B cells, the presumptive progenitors of HL. Consistent with these observations, we found that KDM6B transcriptional targets in GC B cells are enriched...

  7. Herpes simplex virus type 1 gene UL14: phenotype of a null mutant and identification of the encoded protein.

    Science.gov (United States)

    Cunningham, C; Davison, A J; MacLean, A R; Taus, N S; Baines, J D

    2000-01-01

    Herpes simplex virus type 1 (HSV-1) gene UL14 is located between divergently transcribed genes UL13 and UL15 and overlaps the promoters for both of these genes. UL14 also exhibits a substantial overlap of its coding region with that of UL13. It is one of the few HSV-1 genes for which a phenotype and protein product have not been described. Using mass spectrometric and immunological approaches, we demonstrated that the UL14 protein is a minor component of the virion tegument of 32 kDa which is expressed late in infection. In infected cells, the UL14 protein was detected in the nucleus at discrete sites within electron-dense nuclear bodies and in the cytoplasm initially in a diffuse distribution and then at discrete sites. Some of the UL14 protein was phosphorylated. A mutant with a 4-bp deletion in the central region of UL14 failed to produce the UL14 protein and generated small plaques. The mutant exhibited an extended growth cycle at low multiplicity of infection and appeared to be compromised in efficient transit of virus particles from the infected cell. In mice injected intracranially, the 50% lethal dose of the mutant was reduced more than 30,000-fold. Recovery of the mutant from the latently infected sacral ganglia of mice injected peripherally was significantly less than that of wild-type virus, suggesting a marked defect in the establishment of, or reactivation from, latent infection.