A macaque model for AIDS-related oral malignancies

描述（由申请人提供）：由于缺乏相关的动物模型，艾滋病的口腔生物学和与艾滋病相关的口腔并发症的研究受到阻碍。特别是那些毁灭性的恶性肿瘤，比如卡波西氏病 肉瘤（KS）的发展与艾滋病毒诱导的免疫抑制一直难以建模，由于复杂的相互作用，被认为是发生在多种病原体之间。这个探索性项目的目标是建立一个艾滋病相关口腔恶性肿瘤（包括艾滋病-KS）的猿猴模型。这项工作是基于我们发现的猕猴同源的KS相关的 疱疹病毒（KSHV），其被认为是腹膜后纤维瘤病（RF）（猕猴的KS样肿瘤）发展的重要因素。我们已经确定了猕猴疱疹病毒，称为腹膜后纤维瘤病疱疹病毒（RFHV），在猕猴的唾液中，并提出发展战略，从唾液中纯化RFHV和建立细胞感染系统。我们还建议，以确定网站的复制和居住的RFHV在口腔组织。这将与华盛顿国家灵长类动物研究中心（WaNPRC）正在进行的猕猴艾滋病毒预防和治疗策略评估结合进行。其次，我们建议结合WaNPRC的组织分布计划和UW牙科学院口腔健康研究综合中心的细胞培养核心实验室，测试RFHV感染来自口腔组织的原代猕猴和人类细胞培养物的能力。我们的假设是逆转录病毒和疱疹病毒在口腔环境中的相互作用在AIDS-KS/SAIDS-RF的发展中起着重要作用。这项工作的基本原理是提供建立知识共享模式所需的知识库和病毒资源。虽然拟议的研究是探索性的和高风险的，它也是非常重要的，因为它可能会导致一个非常重要的和相关的猕猴模型KS的发展。这种模型可以直接影响这种毁灭性人类疾病的预防，诊断和治疗。

DESCRIPTION (provided by applicant): Research on the oral biology of AIDS and the oral complications associated with AIDS has been hampered by the lack of relevant animal models. In particular, the devastating malignancies, such as Kaposi's Sarcoma (KS) that develop in conjunction with HIV-induced immunosuppression have been difficult to model due to the complicated interactions that are believed to occur between multiple pathogenic agents. The objective for this exploratory project is to develop a simian model for AIDS-related oral malignancies, including AIDS-KS. This work is based on our discovery of the macaque homolog of the KS-associated herpesvirus (KSHV) which is believed to be an important factor in the development of retroperitoneal fibromatosis (RF), a KS-like tumor of macaques. We have identified the macaque herpesvirus, called retroperitoneal fibromatosis herpesvirus (RFHV), in saliva of macaques and propose to develop strategies to purify RFHV from saliva and establish cell infection systems. We also propose to identify the sites of replication and residence of RFHV in oral tissues. This will be done in conjunction with an ongoing evaluation of HIV prevention and therapeutic strategies in macaques at the Washington National Primate Research Center (WaNPRC). Secondly, we propose to test the ability of RFHV to infect primary macaque and human cell cultures derived from oral tissues in conjunction with the Tissue Distribution Program of the WaNPRC and the Cell Culture Core laboratory of the Comprehensive Center for Oral Health Research at the School of Dentistry, UW. Our hypothesis is that interaction of retroviruses and herpesviruses within the oral environment plays an important role in the development of AIDS-KS/SAIDS-RF. The rationale for this work is to provide the knowledge-base and virus resources necessary for the establishment of such a KS model. Although the proposed study is exploratory and high risk, it is also highly significant since it could lead to the development of a very important and relevant macaque model of KS. Such a model could directly impact the prevention, diagnosis, and treatment of this devastating human disease.