Simian homologues of Epstein–Barr virus

Wang, Fred; Rivailler, Pierre; Rao, Pasupuleti Visweswara; Cho, Young-gyu

doi:10.1098/rstb.2000.0776

Cited by 62 publications

(59 citation statements)

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“…Epstein-Barr virus (EBV)-related herpesviruses in the same gamma-1, or lymphocryptovirus (LCV), genera are known to naturally infect both Old and New World nonhuman primates, and the biology of these nonhuman LCVs appears indistinguishable from that of EBV (reviewed in reference 35). The potential utility of using Old World LCV as an animal model system was demonstrated by the ability to experimentally infect naive rhesus macaques with rhesus LCVs and reproduce many aspects of acute and persistent EBV infection in humans (20).…”

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confidence: 99%

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

Rivailler

Jiang

Cho

et al. 2002

J Virol

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119

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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.Epstein-Barr virus (EBV)-related herpesviruses in the same gamma-1, or lymphocryptovirus (LCV), genera are known to naturally infect both Old and New World nonhuman primates, and the biology of these nonhuman LCVs appears indistinguishable from that of EBV (reviewed in reference 35). The potential utility of using Old World LCV as an animal model system was demonstrated by the ability to experimentally infect naive rhesus macaques with rhesus LCVs and reproduce many aspects of acute and persistent EBV infection in humans (20).Previous studies revealed that Old World LCV genomes are organized in a colinear fashion with EBV and that EBV DNA cross-reacts with viral DNA from simian LCVs (11,12). Rhesus LCV homologues for most of the EBV latent infection genes have been described (reviewed in reference 35). In virtually every aspect, these rhesus LCV latent infection genes are functionally interchangeable with the EBV genes despite modest degrees of homology (27 to 50% amino acid homology). However, the gene repertoire from the rhesus LCV, or any gamma-1 herpesvirus besides EBV, has not been completely characterized, particularly those genes encoding cellular homologues and viral glycoproteins that are highly relevant for studies in an animal model system. The development of a rhesus LCV genetic system to generate mutant viruses for use in experimental infections and study of molecular pathogenesis in vivo also requires a thorough understanding of the rhesus LCV genome and its sequence as a starting point.Primary sequence and genome structure of rhesus LCV. Six overlapping cosmid and two plasmid viral DNA clones were isolated from the rhesus LCV-infected B-cell line LCL8664 (Fig. 1A). A shotgun cloning and sequencing strategy was used to derive contiguous sequences from these eight viral DNA clones. The complete rhesus LCV sequence was assembled with a sevenfold average redundancy from 1,500 overlapping sequences of 300 to 800 nucleotides.The rhesus LCV genome contains internal (IR1 to IR4) and terminal repeats (TR) as in EBV (Fig. 1B). The major internal repeat, IR1, contains 5.7 copies of a 3,072-bp motif that is 61.5% homologous to the 3,072-bp BamHI W fragment of the EBV IR1. The rhesus LCV TR consists of a 933-bp motif versus a 538-bp motif in the EBV TR, and there is no significant sequence homology besides a similarly high GC content (75%). Based on 5.7 copies in the major internal repeat and 4 TR copies, the rhesus LCV genome has 171,096 nucleotides (versus 172,231 bp in B95-8 EBV with 11.3 IR1 copies and 4 TR copies), with an overall GC content...

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confidence: 99%

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

Rivailler

Jiang

Cho

et al. 2002

J Virol

Self Cite

119

114

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“…Most animals are infected during infancy through the oral route, and a large majority of the target population is naturally infected by adulthood (29). The virus, which can be detected in blood or upon activation in saliva, persists for life as a latent infection in B cells and immortalizes B cells in tissue culture, and, like EBV, it has been associated with virus-positive B cell lymphomas during immunosuppression (30). Furthermore, rhLCV has a high degree of sequence homology to EBV, molecular organization is well conserved between the two viruses, and they have an identical repertoire of latent and lytic genes (29,31).…”

Section: -Specific Cd8mentioning

confidence: 99%

CD4⁺and CD8⁺T-Cell Responses to Latent Antigen EBNA-1 and Lytic Antigen BZLF-1 during Persistent Lymphocryptovirus Infection of Rhesus Macaques

Leskowitz

Zhou

Villinger

et al. 2013

J Virol

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Epstein-Barr virus (EBV) infection leads to lifelong viral persistence through its latency in B cells. EBV-specific T cells controlreactivations and prevent the development of EBV-associated malignancies in most healthy carriers, but infection can sometimes cause chronic disease and malignant transformation. Epstein-Barr nuclear antigen 1 (EBNA-1) is the only viral protein consistently expressed during all forms of latency and in all EBV-associated malignancies and is a promising target for a therapeutic vaccine. Here, we studied the EBNA-1-specific immune response using the EBV-homologous rhesus lymphocryptovirus (rhLCV) infection in rhesus macaques. We assessed the frequency, phenotype, and cytokine production profiles of rhLCV EBNA-1 (rhEBNA-1)-specific T cells in 15 rhesus macaques and compared them to the lytic antigen of rhLCV BZLF-1 (rhBZLF-1). We were able to detect rhEBNA-1-specific CD4؉ and/or CD8 ؉ T cells in 14 of the 15 animals screened. In comparison, all 15 animals had detectable rhBZLF-1 responses. Most peptide-specific CD4؉ T cells exhibited a resting phenotype of central memory (TCM), while peptide-specific CD8؉ T cells showed a more activated phenotype, belonging mainly to the effector cell subset. By comparing our results to the human EBV immune response, we demonstrate that the rhLCV model is a valid system for studying chronic EBV infection and for the preclinical development of therapeutic vaccines.

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“…Rhesus LCV demonstrates extensive genetic and biological homology to EBV (Wang et al, 2001;Carville and Mansfield, 2008). Orthologous LCVs can be found in a wide variety of other apes and New and Old World monkeys, including the chimpanzee, gorilla, orangutan, baboon, African green monkey, squirrel monkey, capuchin, and marmoset (Pellett and Roizman, 2007).…”

Section: Macaque Lymphocryptovirus Infectionsmentioning

confidence: 99%

Herpesvirus infections of laboratory macaques

Simmons¹

2009

Journal of Immunotoxicology

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Simian homologues of Epstein–Barr virus

Cited by 62 publications

References 58 publications

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

CD4⁺and CD8⁺T-Cell Responses to Latent Antigen EBNA-1 and Lytic Antigen BZLF-1 during Persistent Lymphocryptovirus Infection of Rhesus Macaques

Herpesvirus infections of laboratory macaques

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Simian homologues of Epstein–Barr virus

Cited by 62 publications

References 58 publications

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

CD4+and CD8+T-Cell Responses to Latent Antigen EBNA-1 and Lytic Antigen BZLF-1 during Persistent Lymphocryptovirus Infection of Rhesus Macaques

Herpesvirus infections of laboratory macaques

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CD4⁺and CD8⁺T-Cell Responses to Latent Antigen EBNA-1 and Lytic Antigen BZLF-1 during Persistent Lymphocryptovirus Infection of Rhesus Macaques