Primate Model for Viral Pathogenesis in the Oral Cavity

这是响应PAS-04-066的探索性(R21)应用程序。 口腔的机会性感染，在HIV-1和HIV-2感染者中很常见，但由于缺乏艾滋病相关恶性肿瘤的体内模型，例如伽玛疱疹病毒的重新激活，这一研究一直受到阻碍。狒狒很容易感染HIV-2病毒。我们最近发现，内源性狒狒疱疹病毒(BobonEBV或HVP、BobonKSHV或PapRV2、BobonCMV或PapCMV和BobonHSV或HVP-2)自然存在于口腔中，并在全身免疫抑制时重新激活，引起类似于人类疾病的口腔特异性病理，如口腔毛状白斑和淋巴组织增生。在这里，我们建议从病毒组成、细菌菌群和粘膜生物学(AIM 1)的分子方面进一步描述这一模型，确定对HIV-2急性感染反应的疱疹病毒重新激活频率和口腔内位置(AIM 2)，并检验对HIV-2反应的重新激活是通过与对医源性免疫抑制反应的重新激活进行比较来检验的假设。 目前尚无艾滋病相关恶性肿瘤口腔并发症的临床模型可供实验使用。一个新的灵长类动物模型的特征填补了我们在PAS-04-066中确定的知识的一个重要空白。这项建议充分利用了俄克拉荷马大学现有的由NIH资助的BABON研究资源，并独特地整合了病毒学家、兽医病理学家和口腔病理学家的互补专业知识。

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.