The Experts below are selected from a list of 516 Experts worldwide ranked by ideXlab platform
Fred Wang - One of the best experts on this subject based on the ideXlab platform.
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Non-human Primate Lymphocryptoviruses: Past, Present, and Future
Current topics in microbiology and immunology, 2015Co-Authors: Janine Mühe, Fred WangAbstract:Epstein-Barr virus (EBV) orthologues from non-human primates (NHPs) have been studied for nearly as long as EBV itself. Cross-reactive sera and DNA hybridization studies provided the first glimpses of the closely related herpesviruses that belonged to the same gamma-1 herpesvirus, or Lymphocryptovirus, genus, as EBV. Over the years, detailed molecular and sequence analyses of LCVs that infect humans and other NHPs revealed similar colinear genome structures and homologous viral proteins expressed during latent and lytic infection. Despite these similarities, experimental infection of NHPs with EBV did not result in acute symptoms or persistent infection as observed in humans, suggesting some degree of host species restriction. Genome sequencing and a molecular clone of an LCV isolate from naturally infected rhesus macaques combined with domestic colonies of LCV-naive rhesus macaques have opened the door to a unique experimental animal model that accurately reproduces the normal transmission, acute viremia, lifelong persistence, and immune responses found in EBV-infected humans. This chapter will summarize the advances made over the last 50 years in our understanding of LCVs that naturally infect both Old and New World NHPs, the recent, groundbreaking developments in the use of rhesus macaques as an animal model for EBV infection, and how NHP LCVs and the rhLCV animal model can advance future EBV research and the development of an EBV vaccine.
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Therapeutic Vaccination against the Rhesus Lymphocryptovirus EBNA-1 Homologue, rhEBNA-1, Elicits T Cell Responses to Novel Epitopes in Rhesus Macaques
Journal of virology, 2013Co-Authors: Eduardo Lani Volpe Da Silveira, Fred Wang, Mark H. Fogg, R.m. Leskowitz, Hildegund C.j. Ertl, Roger W. Wiseman, David H. O’connor, Paul M. Lieberman, Francois VillingerAbstract:ABSTRACT Epstein-Barr virus (EBV) is a vaccine/immunotherapy target due to its association with several human malignancies. EBNA-1 is an EBV protein consistently expressed in all EBV-associated cancers. Herein, EBNA-1-specific T cell epitopes were evaluated after AdC–rhEBNA-1 immunizations in chronically Lymphocryptovirus-infected rhesus macaques, an EBV infection model. Preexisting rhEBNA-1-specific responses were augmented in 4/12 animals, and new epitopes were recognized in 5/12 animals after vaccinations. This study demonstrated that EBNA-1-specific T cells can be expanded by vaccination.
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ebv bilf1 evolved to downregulate cell surface display of a wide range of hla class i molecules through their cytoplasmic tail
Journal of Immunology, 2013Co-Authors: Bryan D. Griffin, Maaike E. Ressing, Emmanuel J. H. J. Wiertz, Anna M Gram, Arend Mulder, Daphne Van Leeuwen, Frans H J Claas, Fred WangAbstract:Coevolution of herpesviruses and their hosts has driven the development of both host antiviral mechanisms to detect and eliminate infected cells and viral ploys to escape immune surveillance. Among the immune-evasion strategies used by the Lymphocryptovirus (γ(1)-herpesvirus) EBV is the downregulation of surface HLA class I expression by the virally encoded G protein-coupled receptor BILF1, thereby impeding presentation of viral Ags and cytotoxic T cell recognition of the infected cell. In this study, we show EBV BILF1 to be expressed early in the viral lytic cycle. BILF1 targets a broad range of HLA class I molecules, including multiple HLA-A and -B types and HLA-E. In contrast, HLA-C was only marginally affected. We advance the mechanistic understanding of the process by showing that the cytoplasmic C-terminal tail of EBV BILF1 is required for reducing surface HLA class I expression. Susceptibility to BILF1-mediated downregulation, in turn, is conferred by specific residues in the intracellular tail of the HLA class I H chain. Finally, we explore the evolution of BILF1 within the Lymphocryptovirus genus. Although the homolog of BILF1 encoded by the Lymphocryptovirus infecting Old World rhesus primates shares the ability of EBV to downregulate cell surface HLA class I expression, this function is not possessed by New World marmoset Lymphocryptovirus BILF1. Therefore, this study furthers our knowledge of the evolution of immunoevasive functions by the Lymphocryptovirus genus of herpesviruses.
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summary of roundtable discussion meeting non human primates to assess risk for ebv related lymphomas in humans
Journal of Immunotoxicology, 2012Co-Authors: Thomas T Kawabata, Fred Wang, James L Weave, Dolca Thomas, Marti Rowe, Cris Kamperschroe, Hele G HaggertyAbstract:Epstein-Barr virus (EBV)-associated lymphomas are a known risk for immunosuppressed individuals. Non-clinical methods to determine the potential of new immunomodulatory compounds to produce EBV-associated lymphomas (hazard identification) have not been developed. Since Lymphocryptovirus (LCV) in non-human primates (NHP) has similar characteristics to EBV in humans, a Roundtable meeting was held in October 2010 to explore how the potential for EBV-related lymphomas in humans can be assessed by using surrogate biomarkers for lymphoma risk in NHP toxicity studies. Stakeholders from regulatory agencies, academia, and industry came together to determine the research gaps and potential benefits and considerations of such an approach given the current state-of-the-science. Key conclusions from the discussion included considerations raised about the potential usefulness of LCV-related biomarkers from NHP studies since there is significant controversy over the reliability of using EBV viral load or EBV-specific T-...
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Summary of roundtable discussion meeting: Non-human primates to assess risk for EBV-related lymphomas in humans
Journal of immunotoxicology, 2011Co-Authors: Thomas T Kawabata, Fred Wang, Martin Rowe, Cris Kamperschroer, Dolca Thomas, James L. Weaver, Hele G HaggertyAbstract:Epstein-Barr virus (EBV)-associated lymphomas are a known risk for immunosuppressed individuals. Non-clinical methods to determine the potential of new immunomodulatory compounds to produce EBV-associated lymphomas (hazard identification) have not been developed. Since Lymphocryptovirus (LCV) in non-human primates (NHP) has similar characteristics to EBV in humans, a Roundtable meeting was held in October 2010 to explore how the potential for EBV-related lymphomas in humans can be assessed by using surrogate biomarkers for lymphoma risk in NHP toxicity studies. Stakeholders from regulatory agencies, academia, and industry came together to determine the research gaps and potential benefits and considerations of such an approach given the current state-of-the-science. Key conclusions from the discussion included considerations raised about the potential usefulness of LCV-related biomarkers from NHP studies since there is significant controversy over the reliability of using EBV viral load or EBV-specific T-lymphocytes to predict for lymphoproliferative disorders in transplant patients. In addition, there are technical challenges that need to be further addressed in order to develop methods to measure LCV viral load and LCV-specific T-lymphocytes from cynomolgus monkeys.
Young-gyu Cho - One of the best experts on this subject based on the ideXlab platform.
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Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model
Journal of virology, 2002Co-Authors: Pierre Rivailler, Hua Jiang, Young-gyu Cho, Carol Quink, Fred WangAbstract:We sequenced the rhesus Lymphocryptovirus (LCV) genome in order to determine its genetic similarity to Epstein-Barr virus (EBV). The rhesus LCV encodes a repertoire identical to that of EBV, with 80 open reading frames, including cellular interleukin-10, bcl-2, and colony-stimulating factor 1 receptor homologues and an equivalent set of viral glycoproteins. The highly conserved rhesus LCV gene repertoire provides a unique animal model for the study of EBV pathogenesis.
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Simian homologues of Epstein–Barr virus
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2001Co-Authors: Fred Wang, Pierre Rivailler, Pasupuleti Rao, Young-gyu ChoAbstract:Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to naturally infect Old World non-human primates and are classified in the same Lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share similar biology, and recent studies have demonstrated that these viruses share a similar repertoire of viral genes. Surprisingly, the latent infection genes associated with cell growth transformation demonstrate the most striking sequence divergence, but the functional mechanisms for these genes are generally well conserved. The recent discovery of LCVs naturally infecting New World primates has rewritten the old paradigm of LCV host range restriction to humans and Old World non-human primates, so that these viruses are more widespread than previously believed. However, the New World LCV genome has significant and interesting differences from EBV and other Old World LCVs despite similar biological properties. Thus, the simian homologues of EBV can provide an important animal model for studying LCV pathogenesis, and the similarities and differences that have evolved among these related viruses can provide a unique perspective towards a better understanding of EBV.
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Evolution of Two Types of Rhesus Lymphocryptovirus Similar to Type 1 and Type 2 Epstein-Barr Virus
Journal of virology, 1999Co-Authors: Young-gyu Cho, Alexey V. Gordadze, Paul D. Ling, Fred WangAbstract:Rhesus monkeys and other nonhuman Old World primates are naturally infected with Lymphocryptoviruses (LCV) that are closely related to Epstein-Barr virus (EBV). A rhesus LCV isolate (208-95) was derived from a B-cell lymphoma in a simian immunodeficiency virus-infected rhesus macaque. The EBNA-2 homologues from 208-95 and a previous rhesus LCV isolate (LCL8664) were polymorphic on immunoblotting, so the EBNA-2 genes from these two rhesus LCV were cloned, sequenced, and compared. The EBNA-2 genes have 40% nucleotide and 41% amino acid identities, and the differences are similar to those between the type 1 and type 2 EBV EBNA-2. Sequence from a portion of the LMP1 gene which is extremely divergent among different LCV was virtually identical between the 208-95 and LCL8664 strains, confirming a common rhesus LCV background. Thus, the EBNA-2 polymorphism defines the presence of two different rhesus LCV types, and both rhesus LCV types were found to be prevalent in the rhesus monkey population at the New England Regional Primate Research Center. The existence of two rhesus LCV types suggests that the selective pressure for the evolution of two LCV types is shared by human and nonhuman primate hosts.
Benoît De Thoisy - One of the best experts on this subject based on the ideXlab platform.
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Partial molecular characterisation of New World non-human primate Lymphocryptoviruses.
Infection Genetics and Evolution, 2011Co-Authors: Anne Lavergne, Benoît De Thoisy, Jean-françois Pouliquen, Manuel Ruiz-garcía, Vincent LacosteAbstract:The description of numerous viruses belonging to the Lymphocryptovirus genus from different Old and New World non-human primate species during the past 10 years has led to developing and supporting co-speciational evolution hypotheses for these viruses and their hosts. Among the different primate species tested, only a few were from the New World. This study attempted to achieve a better understanding of the evolutionary processes within the Platyrrhini branch. Molecular screening of 253 blood DNA samples from 20 New World non-human primate species from Central and South America was carried out using polymerase chain reaction amplification with degenerate consensus primers targeting highly conserved amino acid motifs of the herpesvirus DNA polymerase gene. In addition to the 33 samples from which we have already described three Lymphocryptoviruses, amplification products were detected in 17 other samples originating from 11 species (13 sub-species). BLAST searches, pairwise nucleotide and amino acid sequence comparisons, and phylogenetic analyses confirm that they all belong to the Lymphocryptovirus genus. Fourteen distinct Lymphocryptovirus sequences were detected, of which nine have never been reported. Phylogenetic analyses showed that, as expected, the New World virus lineage formed a sister clade to that of the Old World viruses. The parallel determination of the host taxa has demonstrated a good correlation between the distinct monophyletic clades of viruses and the infected primates at the sub-family level. In addition, these results further suggest the existence of two distinct groups within the Cebidae for Saimirinae and Cebinae primates. Nevertheless, based on the current genetic data, this study fell short of achieving a tree that was completely resolved within the lineage of Platyrrhini viruses. Further studies will be needed to better assess the evolutionary relationships between these viruses.
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Genetic diversity and molecular evolution of human and non-human primate Gammaherpesvirinae.
Infection Genetics and Evolution, 2010Co-Authors: Vincent Lacoste, Anne Lavergne, Benoît De Thoisy, Jean-françois Pouliquen, Antoine GessainAbstract:The Gammaherpesvirinae sub-family is divided into two genera: Lymphocryptovirus and Rhadinovirus. Until the middle of the 1990s, the Rhadinovirus genus was only represented by Herpesvirus saimiri and Herpesvirus ateles, which infect New World monkey species. Until the year 2000, Epstein-Barr virus (EBV), the human prototype of the Lymphocryptovirus, and simian homologues had only been detected in humans and Old World non-human primates. It was thought, therefore, that the separation of the continents had resulted in drastic changes in Gammaherpesvirinae evolution. The discovery of Kaposi's sarcoma-associated herpesvirus in humans, belonging to the Rhadinovirus, followed by the identification of CalHV3 (Callitrichine herpesvirus 3), a Lymphocryptovirus of the marmoset, challenged this paradigm. The description of numerous viruses belonging to this sub-family from various Old and New World primate species enabled a cospeciation hypothesis for these viruses and their hosts to be developed. This review focuses on the current knowledge of primate Gammaherpesvirinae genetic diversity and molecular evolution. We discuss the various theories based on current genetic data regarding evolutionary relationships between Lymphocryptoviruses of Old World primates, the use of these data as a tool to study evolutionary relationships between New World monkey species, and the possible existence of a ninth human herpesvirus belonging to the Rhadinovirus genus.
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diversite genetique et evolution des gammaherpesvirinae de primates
Virologie, 2007Co-Authors: Vincent Lacoste, Anne Lavergne, Benoît De Thoisy, Jean-françois Pouliquen, Antoine GessainAbstract:La sous-famille des Gammaherpesvirinae est divisee en deux genres, le genre des Lymphocryptovirus et le genre des Rhadinovirus. Jusque recemment, le virus d’Epstein-Barr (EBV), prototype humain des Lymphocryptovirus, et les virus simiens associes n’avaient ete trouves que chez des primates humains et non humains de l’ancien monde. Le genre des Rhadinovirus n’etait, lui, represente que par les herpesvirus saimiri et atele infectant deux especes de primate du nouveau monde. De ce fait, le modele etabli etait que la separation ancien-nouveau monde avait apporte des changements drastiques dans l’evolution des Gammaherpesvirinae. La decouverte de l’herpesvirus humain 8 (HHV8) chez l’homme, appartenant au genre des Rhadinovirus puis celle d’un Lymphocryptovirus chez le ouistiti, CalHV3, sont venus remettre en cause ce vieux paradigme. La description recente de nombreux autres virus appartenant a cette sous-famille des Gammaherpesvirinae, a partir de differentes especes de primates non humains de l’ancien et du nouveau monde, a permis de developper puis de soutenir des hypotheses de co-evolution entre ces virus et leurs hotes. Cette revue fait le point des connaissances actuelles concernant la diversite genetique et l’evolution des Gammaherpesvirinae de primates.
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Novel gamma-1 herpesviruses identified in free-ranging New World monkeys (golden-handed tamarin [Saguinus midas], squirrel monkey [Saimiri sciureus],and white-faced saki [Pithecia pithecia]) in French Guiana
Journal of virology, 2003Co-Authors: Benoît De Thoisy, Jean-françois Pouliquen, Vincent Lacoste, Antoine Gessain, Mirdad KazanjiAbstract:The recent finding of a novel Epstein-Barr virus-related Lymphocryptovirus (CalHV-3) in a captive colony of common marmoset (Callithrix jacchus) in the United States modifies the view that the host range of Lymphocryptovirus is restricted to humans and Old World primates. We investigated the presence of Epstein-Barr virus-related viruses in 79 samples of New World monkeys caught in the wild, including six species of the Cebidae family and one of the Callitrichidae, living in the rain forest of French Guiana. Using a degenerate consensus PCR method for the herpesvirus DNA polymerase gene, we identified three novel Lymphocryptoviruses from golden-handed tamarin (Saguinus midas) of the Callitrichidae family and squirrel monkey (Saimiri sciureus) and white-faced saki (Pithecia pithecia) of the Cebidae family. With the CalHV-3 strain, these three novel viruses constitute a well-supported phylogenetic clade in the Lymphocryptovirus genus, which is clearly distinct from the lineage of Old World Lymphocryptovirus, hosted by catarrhine monkeys and humans. In tamarins, the prevalence of the novel Lymphocryptovirus was more than 50%, indicating that it circulates well in the wild population, perhaps due to specific ecoethological patterns such as confrontations and intergroup migration. The detection and partial molecular characterization of the polymerase gene of three novel Gamma-1-Herpesvirinae from New World monkeys caught in the wild clearly indicate that free-ranging populations of platyrrhine are natural hosts of Lymphocryptoviruses. Further characterization of these novel viruses will provide new insight not only into the origin and evolution of Gammaherpesvirinae but also into their pathogenicity.
Bernhard Ehlers - One of the best experts on this subject based on the ideXlab platform.
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Lymphocryptovirus phylogeny and the origins of Epstein-Barr virus.
The Journal of general virology, 2009Co-Authors: Bernhard Ehlers, Katja Spiess, Fabian Leendertz, Martine Peeters, Christophe Boesch, Derek Gatherer, Duncan J McgeochAbstract: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 Lymphocryptoviruses (LCVs) are now known, with hosts from six primate families (Hominidae, Hylobatidae, Cercopithecidae, Atelidae, Cebidae and Pitheciidae). Further work extended genomic sequences for 25 LCVs to 3.4-7.4 kbp. Phylogenetic trees were constructed, based on alignments of protein sequences inferred from the LCV genomic data. The LCVs fell into three major clades: Clade A, comprising New World viruses; Clade B, containing both Old World monkey viruses and hominoid viruses including Epstein-Barr virus (EBV); and Clade C, containing other hominoid viruses. By comparison with the primate tree, it was proposed that major elements of the LCV tree represented synchronous evolution with host lineages, with the earliest node in both trees being the separation of Old and New World lines, but that some virus lineages originated by interspecies transfer. From comparisons of branch lengths, it was inferred that evolutionary substitution in Clade B has proceeded more slowly than elsewhere in the LCV tree. It was estimated that in Clade B a subclade containing EBV, a gorilla virus and two chimpanzee viruses derived from an Old World monkey LCV line approximately 12 million years ago, and another subclade containing an orang-utan virus and a gibbon virus derived from a macaque LCV line approximately 1.2 million years ago.
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Lymphocryptovirus phylogeny and the origins of Epstein–Barr virus
Journal of General Virology, 2009Co-Authors: Bernhard Ehlers, Katja Spiess, Fabian Leendertz, Martine Peeters, Christophe Boesch, Derek Gatherer, Duncan J McgeochAbstract: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 Lymphocryptoviruses (LCVs) are now known, with hosts from six primate families (Hominidae, Hylobatidae, Cercopithecidae, Atelidae, Cebidae and Pitheciidae). Further work extended genomic sequences for 25 LCVs to 3.4-7.4 kbp. Phylogenetic trees were constructed, based on alignments of protein sequences inferred from the LCV genomic data. The LCVs fell into three major clades: Clade A, comprising New World viruses; Clade B, containing both Old World monkey viruses and hominoid viruses including Epstein-Barr virus (EBV); and Clade C, containing other hominoid viruses. By comparison with the primate tree, it was proposed that major elements of the LCV tree represented synchronous evolution with host lineages, with the earliest node in both trees being the separation of Old and New World lines, but that some virus lineages originated by interspecies transfer. From comparisons of branch lengths, it was inferred that evolutionary substitution in Clade B has proceeded more slowly than elsewhere in the LCV tree. It was estimated that in Clade B a subclade containing EBV, a gorilla virus and two chimpanzee viruses derived from an Old World monkey LCV line approximately 12 million years ago, and another subclade containing an orang-utan virus and a gibbon virus derived from a macaque LCV line approximately 1.2 million years ago.
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Discovery of herpesviruses in multi-infected primates using locked nucleic acids (LNA) and a bigenic PCR approach
Virology Journal, 2007Co-Authors: Sandra Prepens, Karl-anton Kreuzer, Fabian Leendertz, Andreas Nitsche, Bernhard EhlersAbstract:Targeting the highly conserved herpes DNA polymerase (DPOL) gene with PCR using panherpes degenerate primers is a powerful tool to universally detect unknown herpesviruses. However, vertebrate hosts are often infected with more than one herpesvirus in the same tissue, and pan-herpes DPOL PCR often favors the amplification of one viral sequence at the expense of the others. Here we present two different technical approaches that overcome this obstacle: (i) Pan-herpes DPOL PCR is carried out in the presence of an oligonucleotide substituted with locked nucleic acids (LNA).This suppresses the amplification of a specific herpesvirus DPOL sequence by a factor of approximately 1000, thereby enabling the amplification of a second, different DPOL sequence. (ii) The less conserved glycoprotein B (gB) gene is targeted with several sets of degenerate primers that are restricted to gB genes of different herpesvirus subfamilies or genera. These techniques enable the amplification of gB and DPOL sequences of multiple viruses from a single specimen. The partial gB and DPOL sequences can be connected by long-distance PCR, producing final contiguous sequences of approximately 3.5 kbp. Such sequences include parts of two genes and therefore allow for a robust phylogenetic analysis. To illustrate this principle, six novel herpesviruses of the genera Rhadinovirus, Lymphocryptovirus and Cytomegalovirus were discovered in multi-infected samples of non-human primates and phylogenetically characterized.
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Novel simian homologues of Epstein-Barr virus
Journal of virology, 2003Co-Authors: Bernhard Ehlers, Fabian Leendertz, Christophe Boesch, Andreas Ochs, Michael Goltz, Kerstin Mätz-rensingAbstract:Thirty different Lymphocryptoviruses (LCV), 26 of them novel, were detected in primates by a panherpesvirus PCR assay. Nineteen LCV from chimpanzees, bonobos, gorillas, and other Old World primates were closely related to Epstein-Barr virus (EBV), the type species of the genus Lymphocryptovirus. Seven LCV originating from New World primates were related to callitrichine herpesvirus 3 (CalHV-3), the first recognized New World LCV. Importantly, a second LCV from gorillas and three LCV from orangutans and gibbons were only distantly related to EBV and CalHV-3. They were tentatively assigned to a novel genogroup of Old World primate LCV. The work described in the paper may also help identify an as yet unknown human LCV.
Pierre Rivailler - One of the best experts on this subject based on the ideXlab platform.
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Experimental rhesus Lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host
Blood, 2004Co-Authors: Pierre Rivailler, Susan V Westmoreland, Carol Quink, Angela Carville, Amitinder Kaur, Jeffery L. Kutok, Sherry Klumpp, Meredith A. Simon, Pasupuleti Rao, Jon C. AsterAbstract:To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P-infected, immunosuppressed rhesus macaques with the EBV-related rhesus Lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4 immunocompetent animals was characterized by an acute viremia and seroconversion followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected orally with LCV failed to develop an LCV-specific humoral response and viremia was more pronounced, but there was no evidence of LCV-induced lymphoproliferative disease. A more aggressive primary challenge was administered by intravenous inoculation of 10(8) autologous, LCV-immortalized B cells in 4 additional immunosuppressed animals. Two animals with modest immunosuppression remained asymptomatic, and 1 of 2 severely immunosuppressed animals developed an aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease.
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Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model
Journal of virology, 2002Co-Authors: Pierre Rivailler, Hua Jiang, Young-gyu Cho, Carol Quink, Fred WangAbstract:We sequenced the rhesus Lymphocryptovirus (LCV) genome in order to determine its genetic similarity to Epstein-Barr virus (EBV). The rhesus LCV encodes a repertoire identical to that of EBV, with 80 open reading frames, including cellular interleukin-10, bcl-2, and colony-stimulating factor 1 receptor homologues and an equivalent set of viral glycoproteins. The highly conserved rhesus LCV gene repertoire provides a unique animal model for the study of EBV pathogenesis.
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Simian homologues of Epstein–Barr virus
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2001Co-Authors: Fred Wang, Pierre Rivailler, Pasupuleti Rao, Young-gyu ChoAbstract:Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to naturally infect Old World non-human primates and are classified in the same Lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share similar biology, and recent studies have demonstrated that these viruses share a similar repertoire of viral genes. Surprisingly, the latent infection genes associated with cell growth transformation demonstrate the most striking sequence divergence, but the functional mechanisms for these genes are generally well conserved. The recent discovery of LCVs naturally infecting New World primates has rewritten the old paradigm of LCV host range restriction to humans and Old World non-human primates, so that these viruses are more widespread than previously believed. However, the New World LCV genome has significant and interesting differences from EBV and other Old World LCVs despite similar biological properties. Thus, the simian homologues of EBV can provide an important animal model for studying LCV pathogenesis, and the similarities and differences that have evolved among these related viruses can provide a unique perspective towards a better understanding of EBV.
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Strong Selective Pressure for Evolution of an Epstein-Barr Virus LMP2B Homologue in the Rhesus Lymphocryptovirus
Journal of virology, 1999Co-Authors: Pierre Rivailler, Carol Quink, Fred WangAbstract:Latent membrane protein 2B (LMP2B) is expressed during latent Epstein-Barr virus (EBV) infection, but little is known about its role. The goal of this study was to determine whether an LMP2B homologue is conserved in the rhesus monkey Lymphocryptovirus (LCV). Both rhesus LCV LMP2A and LMP2B genes were cloned and sequenced. The rhesus LCV LMP2B gene is positionally conserved, and the EBNA-2 responsiveness and the bidirectional nature of the LMP1-LMP2B promoter have also been functionally conserved. However, this region of the genome encoding the LMP1, LMP1-LMP2B promoter, and LMP2B first exon demonstrates the most dramatic nucleotide sequence divergence between human and nonhuman LCV observed to date. Evolution of the rhesus LCV LMP2B promoter and transcript despite the dynamic nature of this genomic region reflects strong selective pressure for a yet-to-be-identified LMP2B function.
