| The gamma-herpesviruses, Epstein Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV), comprise a unique class within the herpesviridae with the ability to infect and persist in a latent state within the lymphocyte population of primates and other animals. They are also unique in their association with malignant phenotypes including Hairy leukoplakia, Burkitt's lymphoma and post-transplant lymphoma for EBV; and Kaposi's sarcoma, Primary effusion lymphoma, and Multicentric Castleman's disease for KSHV. Reactivation of these viruses and their associated malignancies cause significant morbidity and mortality in HIV infected individuals and immunosuppressed transplant recipients. To understand gamma-herpesvirus biology it is useful to investigate closely related gamma-herpesviruses of non-human primates. It is known that baboons carry the EBV homologue Herpesvirus papio. Here I report evidence for a novel KSHV homologue in captive baboon species. Using degenerate PCR a novel rhadinovirus, PapRV2, was identified having substantial sequence identity to two essential KSHV genes, the viral polymerase and thymidylate synthase. A subset of animals exhibit detectable PapRV2 viral load in PBMCs. Extensive serological analysis of nearly 200 animals demonstrated that the majority carried cross-reacting antibodies that recognize KSHV or macaque rhadinovirus antigens. Seroreactivity increased with age similar to the age specific prevalence of KSHV in the human population. This establishes baboons as a novel resource to investigate gamma-herpesvirus biology.;I employed the baboon model to investigate the reactivation patterns of two herpesvirus lineages, beta and gamma, simultaneously in vivo . Systemic viral loads oscillated rather than increasing monotonously during constant iatrogenic immunosuppression. The viral loads for PapRV2 and HVP changed synchronously, while the viral loads for the baboon beta herpesvirus BaCMV oscillated independently, suggesting that the physiological reactivation triggers are different for each virus. I observed maximal BaCMV viral loads in salivary gland, consistent with the biology of human CMV. PapRV2 was found in circulating B-cells and associated with lymphoproliferative disease. I also encountered post-transplant lymphoma disease (PTLD) and, for the first time, oral hairy leukoplakia, a signature complication of EBV reactivation in AIDS patients. This study validates baboons as an appropriate non-human primate model in which to study poly-microbial interactions during immunodeficiency. |
