This resource-related (R24) grant proposes to characterize the two distinct lineages of macaque rhadinovirus related to human herpesvirus 8 (HHV8), RV1 and RV2. New reagents and assays have been developed to study the latency and reactivation of these viruses in macaque models of human disease. Our proposed studies initially focus on the rhadinoviruses of the pig-tailed macaque, the most common macaque species maintained at the Washington National Primate Research Center. The macaque rhadinoviruses are highly prevalent in captive macaque populations and express viral proteins that interact with host cellular proteins, including those affecting the host immune system. Thus, the presence of these viruses may complicate and/or confound the interpretation of data from macaque models of human disease. The potential for interference may be most acute in macaque models of immunosuppression. Both RV1 and RV2 have been associated with significant diseases in macaques that closely resemble cancers associated with HHV8 in humans, including Kaposi sarcoma (KS), lymphoma and multicentric Castleman's disease. Thus, the characterization of the macaque rhadinoviruses, including the development of specific reagents and assays that enable the evaluation of their biology and life cycles, is an important prerequisite for the development of herpesvirus-related macaque models and to the successful use of macaques as models of other diseases. Specifically, we propose to 1) Complete the genomic sequence of the macaque RV1 rhadinovirus, RFHVMn, 2) Develop specific assays to study the infection and prevalence of the macaque RV1 and RV2rhadinoviruses, 3) Characterize the experimental infection of naive macaques with RV1 and RV2rhadinoviruses in vivo, and 4) Characterize the reactivation of existing latent infections of RV1 and RV2rhadinoviruses in macaques by treatment with immunosuppressive agents.
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