This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rhesus lymphocryptovirus (RhLCV) is genetically similar to EBV, and results in persistent latent infection in rhesus macaques. The Glycine-Alanine repeat GAr domain of RhLCV EBNA1 is condensed and unlike EBV EBNA1 does not inhibit antigen processing. In order to determine the CTL repertoire in RhLCV infected rhesus macaques, we measured the frequency of interferon-g-secreting peripheral blood mononuclear cells responding to stimulation with vaccinia recombinants expressing the RhLCV EBNA1, 2, 3A, 3B, 3C, LP and portions of LMP1 and 2 proteins by ELISPOT assays. In addition, T cell responses to rhBZLF1 were measured in order to determine the contribution of lytic proteins to the LCV-specific cellular immune response. BZLF1-specific ELISPOT responses were frequently detected in naturally rhLCV-infected rhesus macaques and were of higher magnitude compared to the response to latent proteins. Among latent proteins, EBNA1 appeared to be immunodominant. Analysis of restimulated PBMCs using peptides derived from RhLCV EBNA1 protein confirmed the abundance of EBNA1 specific CTLs in rhesus macaques, but these CTLs were unable to recognize endogenously expressed full length EBNA1 protein. These data suggest that an immune evasion mechanism has been conserved in the rhesus LCV EBNA1 and rhesus LCV, and thus provides an ideal model in which to study the immune evasion mechanisms of EBV-related herpesviruses in vivo. The identification of BZLF1 as a dominant target for CTL further supports the use of this model to study pathogenesis of EBV infection.
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