Primate Model for Viral Pathogenesis in the Oral Cavity

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

This is an exploratory (R21) application in response to PAS-04-066. Opportunistic infections of the oral cavity and frequent in HIV-1 and HIV-2 infected individuals, but research has been hampered by a lack of adaequte in vivo models of AIDS-associated malignancies, such as caused by reactivation of gamma herpesvirueses. Baboons are susceptible to HIV-2 infection. We have recently shown that endogenous baboon herpesviruses (BaboonEBV or HVP, BaboonKSHV or PapRV2, BaboonCMV or PapCMV and BaboonHSV or HVP-2) are naturally present in the oral cavity, reactivate in response to systemic immunosupression and cause oral-specific pathology similar to the human disease, such as oral-hairy-leukoplakia and lymphoid-hyperplasia. Here, we propose to further characterize this model in molecular terms with respect to virus composition, bacterial flora and mucosal biology (AIM 1), determine herpesvirus reactivation frequency and intra-oral location in response to accute HIV-2 infection (AIM 2), and test the hypothesis that reactivation in response to HIV-2 is exagerated by comparison to reactivation in response to iatrogenic immunosuppression. Currently there are no experimentally accessible clinical models for oral complications of AIDS-associated malignacies. The characterization of a new primate model fills an important gap in our knowledge as identified in PAS-04-066. This proposal capitalizes upon the existing NIH-funded Baboon research resource at the University of Oklahoma and uniquely integrates the complementary expertise of virologists, veterinary pathologists and oral pathologists.