The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Nancy Raab-traub - One of the best experts on this subject based on the ideXlab platform.
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Rhesus Lymphocryptovirus latent membrane protein 2A activates β-catenin signaling and inhibits differentiation in epithelial cells
Virology, 2008Co-Authors: Catherine A. Siler, Nancy Raab-traubAbstract:Abstract Rhesus Lymphocryptovirus (LCV) is a γ-herpesvirus closely related to Epstein–Barr virus (EBV). The Rhesus latent membrane protein 2A (LMP2A) is highly homologous to EBV LMP2A. EBV LMP2A activates the phosphatidylinositol 3-kinase (PI3K) and β-catenin signaling pathways in epithelial cells and affects differentiation. In the present study, the biochemical and biological properties of Rhesus LMP2A in epithelial cells were investigated. The expression of Rhesus LMP2A in epithelial cells induced Akt activation, GSK3β inactivation and accumulation of β-catenin in the cytoplasm and nucleus. The nuclear translocation, but not accumulation of β-catenin was dependent on Akt activation. Rhesus LMP2A also impaired epithelial cell differentiation; however, this process was not dependent upon Akt activation. A mutant Rhesus LMP2A lacking six transmembrane domains functioned similarly to wild-type Rhesus LMP2A indicating that the full number of transmembrane domains is not required for effects on β-catenin or cell differentiation. These results underscore the similarity of LCV to EBV and the suitability of the macaque as an animal model for studying EBV pathogenesis.
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Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed.
PLoS pathogens, 2006Co-Authors: Xuezhong Cai, Ronald C. Desrosiers, Alexandra Schäfer, John P. Bilello, Rachel Hood Edwards, Nancy Raab-traub, Bryan R. CullenAbstract:The pathogenic Lymphocryptovirus Epstein-Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus Lymphocryptovirus, which is separated from EBV by > or =13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, Lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues.
Catherine A. Siler - One of the best experts on this subject based on the ideXlab platform.
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Rhesus Lymphocryptovirus latent membrane protein 2A activates β-catenin signaling and inhibits differentiation in epithelial cells
Virology, 2008Co-Authors: Catherine A. Siler, Nancy Raab-traubAbstract:Abstract Rhesus Lymphocryptovirus (LCV) is a γ-herpesvirus closely related to Epstein–Barr virus (EBV). The Rhesus latent membrane protein 2A (LMP2A) is highly homologous to EBV LMP2A. EBV LMP2A activates the phosphatidylinositol 3-kinase (PI3K) and β-catenin signaling pathways in epithelial cells and affects differentiation. In the present study, the biochemical and biological properties of Rhesus LMP2A in epithelial cells were investigated. The expression of Rhesus LMP2A in epithelial cells induced Akt activation, GSK3β inactivation and accumulation of β-catenin in the cytoplasm and nucleus. The nuclear translocation, but not accumulation of β-catenin was dependent on Akt activation. Rhesus LMP2A also impaired epithelial cell differentiation; however, this process was not dependent upon Akt activation. A mutant Rhesus LMP2A lacking six transmembrane domains functioned similarly to wild-type Rhesus LMP2A indicating that the full number of transmembrane domains is not required for effects on β-catenin or cell differentiation. These results underscore the similarity of LCV to EBV and the suitability of the macaque as an animal model for studying EBV pathogenesis.
Fred Wang - One of the best experts on this subject based on the ideXlab platform.
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cloning of the epstein barr virus related Rhesus Lymphocryptovirus as a bacterial artificial chromosome a loss of function mutation of the rhbarf1 immune evasion gene
Journal of Virology, 2011Co-Authors: Makoto Ohashi, Carol Quink, Nina Orlova, Fred WangAbstract:Rhesus macaques are naturally infected with a gammaherpesvirus which is in the same Lymphocryptovirus (LCV) genus as and closely related to Epstein-Barr virus (EBV). The Rhesus macaque LCV (rhLCV) contains a repertoire of genes identical to that of EBV, and experimental rhLCV infection of naive Rhesus macaques accurately models acute and persistent EBV infection of humans. We cloned the LCL8664 rhLCV strain as a bacterial artificial chromosome to create recombinant rhLCV for investigation in this animal model system. A recombinant rhLCV (clone 16 rhLCV) carrying a mutation in the putative immune evasion gene rhBARF1 was created along with a rescued wild-type (rWT) rhLCV in which the rhBARF1 open reading frame (ORF) was repaired. The rWT rhLCV molecular clone demonstrated viral replication and B-cell immortalization properties comparable to those of the naturally derived LCL8664 rhLCV. Qualitatively, clone 16 rhLCV carrying a mutated rhBARF1 was competent for viral replication and B-cell immortalization, but quantitative assays showed that clone 16 rhLCV immortalized B cells less efficiently than LCL8664 and rWT rhLCV. Functional studies showed that rhBARF1 could block CSF-1 cytokine signaling as well as EBV BARF1, whereas the truncated rhBARF1 from clone 16 rhLCV was a loss-of-function mutant. These recombinant rhLCV can be used in the Rhesus macaque animal model system to better understand how a putative viral immune evasion gene contributes to the pathogenesis of acute and persistent EBV infection. The development of a genetic system for making recombinant rhLCV constitutes a major advance in the study of EBV pathogenesis in the Rhesus macaque animal model.
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cloning of the Rhesus Lymphocryptovirus viral capsid antigen and epstein barr virus encoded small rna homologues and use in diagnosis of acute and persistent infections
Journal of Clinical Microbiology, 2000Co-Authors: Pasupuleti Rao, Hua Jiang, Fred WangAbstract:Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with the development of several human malignancies. A closely related herpesvirus in the same Lymphocryptovirus (LCV) genera as EBV naturally infects Rhesus monkeys and provides an important animal model for studying EBV pathogenesis. We cloned the small viral capsid antigen (sVCA) homologue from the Rhesus LCV and developed a peptide enzyme-linked immunosorbent assay (ELISA) to determine whether epitopes in the Rhesus LCV sVCA are a reliable indicator of Rhesus LCV infection. In order to define a “gold standard” for Rhesus LCV infection, we also cloned the EBV-encoded small RNA 1 (EBER1) and EBER2 homologues from Rhesus LCV and developed a reverse transcription (RT)-PCR assay to detect persistent LCV infection in Rhesus monkey peripheral blood lymphocytes. Animals from a conventional and a hand-reared colony were studied to compare the prevalence of Rhesus LCV infection in the two groups. There was a 100% correlation between the peptide ELISA and EBER RT-PCR results for Rhesus LCV infection. In addition, specificity for LCV infection and exclusion of potential cross-reactivity to the Rhesus rhadinovirus sVCA homologue could be demonstrated using sera from experimentally infected animals. These studies establish two novel assays for reliable diagnosis of acute and persistent Rhesus LCV infections. The Rhesus LCV sVCA peptide ELISA provides a sensitive and reliable assay for routine screening, and these studies of the hand-reared colony confirm the feasibility of raising Rhesus LCV-naive animals.
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Structural, Functional, and Genetic Comparisons of Epstein-Barr Virus Nuclear Antigen 3A, 3B, and 3C Homologues Encoded by the Rhesus Lymphocryptovirus
Journal of virology, 2000Co-Authors: Hua Jiang, Young-gyu Cho, Fred WangAbstract:EBNA-3A, -3B, and -3C are three latent infection nuclear proteins important for Epstein-Barr virus (EBV)-induced B-cell immortalization and the immune response to EBV infection. All three are hypothesized to function as transcriptional transactivators, but little is known about their precise mechanism of action or their role in EBV pathogenesis. We have cloned and studied the three EBNA-3 homologues from a closely related Lymphocryptovirus (LCV) which naturally infects Rhesus monkeys. The Rhesus LCV EBNA-3A, -3B, and -3C homologues have 37, 40, and 36% amino acid identity with the EBV genes, respectively. Function, as measured by in vitro assays, also appears to be conserved with the EBV genes, since the Rhesus LCV EBNA-3s can interact with the transcription factor RBP-Jκ and the Rhesus LCV EBNA-3C encodes a Q/P-rich domain with transcriptional activation properties. In order to better understand the relationship between these EBV and Rhesus LCV latent infection genes, we asked if the Rhesus LCV EBNA-3 locus could be recombined into the EBV genome and if it could substitute for the EBV EBNA-3s when assayed for human B-cell immortalization. Recombination between the EBV genome and Rhesus LCV DNA was reasonably efficient. However, these studies suggest that the Rhesus LCV EBNA-3 locus was not completely interchangeable with the EBV EBNA-3 locus for B-cell immortalization and that at least one determinant of the species restriction for LCV-induced B-cell immortalization maps to the EBNA-3 locus. The overall conservation of EBNA-3 structure and function between EBV and Rhesus LCV indicates that Rhesus LCV infection of Rhesus monkeys can provide an important animal model for studying the role of the EBNA-3 genes in LCV pathogenesis.
Jeffrey I. Cohen - One of the best experts on this subject based on the ideXlab platform.
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Soluble Rhesus Lymphocryptovirus gp350 Protects against Infection and Reduces Viral Loads in Animals that Become Infected with Virus after Challenge
2013Co-Authors: Junji Sashihara ¤a, Yo Hoshino ¤b, Jason J. Bowman, Tammy Krogmann, Peter D. Burbelo, V. Mcneil, Kurt Kamrud ¤d, Jeffrey I. CohenAbstract:Epstein-Barr virus (EBV) is a human Lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350) or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]). No comparative trials, however, have been performed. Rhesus Lymphocryptovirus (LCV) encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated Rhesus monkeys at 0, 4 and 12 weeks with (a) soluble Rhesus LCV gp350, (b) virus-like replicon particles (VRPs) expressing Rhesus LCV gp350, (c) VRPs expressing Rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d) PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with Rhesus LCV, animals vaccinated with soluble Rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LC
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Soluble Rhesus Lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.
Public Library of Science (PLoS), 2011Co-Authors: Junji Sashihara, Jason J. Bowman, Tammy Krogmann, Peter D. Burbelo, Yo Hoshino, Mcneil V Coffield, Kurt Kamrud, Jeffrey I. CohenAbstract:Epstein-Barr virus (EBV) is a human Lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350) or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]). No comparative trials, however, have been performed. Rhesus Lymphocryptovirus (LCV) encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated Rhesus monkeys at 0, 4 and 12 weeks with (a) soluble Rhesus LCV gp350, (b) virus-like replicon particles (VRPs) expressing Rhesus LCV gp350, (c) VRPs expressing Rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d) PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with Rhesus LCV, animals vaccinated with soluble Rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with Rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with other EBV proteins, should be considered to reduce EBV infection or virus-associated malignancies in humans
Bryan R. Cullen - One of the best experts on this subject based on the ideXlab platform.
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Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed.
PLoS pathogens, 2006Co-Authors: Xuezhong Cai, Ronald C. Desrosiers, Alexandra Schäfer, John P. Bilello, Rachel Hood Edwards, Nancy Raab-traub, Bryan R. CullenAbstract:The pathogenic Lymphocryptovirus Epstein-Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus Lymphocryptovirus, which is separated from EBV by > or =13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, Lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues.