Primate Model for Viral Pathogenesis in the Oral Cavity

这是响应PAS-04-066的探索性（R21）应用。 艾滋病是口腔内的恶性感染，常见于HIV-1和HIV-2感染者，但由于缺乏合适的艾滋病相关恶性肿瘤体内模型，如γ疱疹病毒再活化引起的恶性肿瘤，研究受到阻碍。狒狒易受HIV-2感染。我们最近发现内源性狒狒疱疹病毒（BaboonEBV或HVP、BaboonKSHV或PapRV 2、BaboonCMV或PapCMV和BaboonHSV或HVP-2）天然存在于口腔中，响应于全身性免疫抑制而重新激活，并引起类似于人类疾病的口腔特异性病理学，如口腔毛状白斑和淋巴样增生。在这里，我们建议进一步表征该模型在分子方面的病毒组成，细菌植物群和粘膜生物学（AIM 1），确定疱疹病毒的再激活频率和口腔内的位置，以应对急性HIV-2感染（AIM 2），并测试的假设，即再激活响应HIV-2是通过比较，再激活响应医源性免疫抑制。 目前，还没有实验性的临床模型，用于艾滋病相关的口腔并发症。新灵长类动物模型的表征填补了PAS-04-066中确定的知识空白。该提案利用了俄克拉荷马州大学现有的NIH资助的狒狒研究资源，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.