Inhibition of antigen presentation by the glycine/alanine repeat domain isnot conserved in simian homologues of Epstein-Barr virus nuclear antigen 1

Most humans and Old World nonhuman primates are infected for life with Epst ein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymp hocryptoviros (LCV) subgroup. Several potential strategies for immune evasi on and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experim entally. Interest has focused an the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal vi ral genome in latently infected cells and because EBNA1 endogenously expres sed in these cells is protected from presentation to the major histocompati bility complex class-I restricted cytotoxic T-lymphocyte (CTL) response thr ough the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old Wor ld primates, we hypothesized that strategies essential for viral persistenc e would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-depe ndent plasmid maintenance and replication. Interestingly, all three LCVs po ssess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibi t antigen processing and presentation as determined by using three differen t in vitro CTL assays. These studies suggest that inhibition of antigen pro cessing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be impor tant for immune evasion during LCV infection.