Primate Model for Viral Pathogenesis in the Oral Cavity

口腔病毒发病机制的灵长类动物模型

• 批准号: 7108542
• 负责人: Dirk P Dittmer
• 金额: $ 25.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7108542
• 关键词: Gammaherpesvirinae; HIV infections; Herpesviridae disease; artificial immunosuppression; baboons; disease /disorder model; human immunodeficiency virus 2; latent virus infection; mouth; opportunistic infections; oral bacteria; oral mucosa; virus infection mechanism

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.

这是响应 PAS-04-066 的探索性 (R21) 应用程序。 口腔机会性感染在 HIV-1 和 HIV-2 感染者中很常见，但由于缺乏与艾滋病相关的恶性肿瘤（例如由伽马疱疹病毒重新激活引起的恶性肿瘤）的适当体内模型，研究受到了阻碍。狒狒很容易感染 HIV-2。我们最近发现，内源性狒狒疱疹病毒（BaboonEBV 或 HVP、BaboonKSHV 或 PapRV2、BaboonCMV 或 PapCMV 和 BaboonHSV 或 HVP-2）天然存在于口腔中，响应全身免疫抑制而重新激活，并引起与人类疾病相似的口腔特异性病理，例如口腔毛白斑和 淋巴组织增生。在这里，我们建议在病毒组成、细菌菌群和粘膜生物学（AIM 1）方面进一步从分子角度描述该模型，确定针对急性 HIV-2 感染的疱疹病毒再激活频率和口腔内位置（AIM 2），并检验以下假设：与医源性免疫抑制的再激活相比，对 HIV-2 的再激活被夸大。 目前，还没有针对艾滋病相关恶性肿瘤口腔并发症的实验可用的临床模型。新灵长类动物模型的表征填补了 PAS-04-066 中确定的我们知识中的一个重要空白。该提案利用了俄克拉荷马大学现有的 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。