Animal Model Core

该计划项目对艾滋病毒潜伏期和病毒库的机制进行全面分析。组织培养系统中的体外研究（项目1、2和3）将与该核心中的体内研究（“非人灵长类动物的HIV/SIV储库和潜伏期”）密切协调。因此，该核心将为本计划项目中的动物模型研究提供恒河猴和适当的基础设施支持。这个核心使用的猕猴被安置在加州大学戴维斯分校的加州国家灵长类动物研究中心（CNPRC）。该中心由美国实验动物护理认证协会（AAALAC）认证，包括全职持牌兽医。适当的设施和 在生物安全等级2和3（BSL-2，-3）下，可获得护理和处理接种SIV/SHIV的猕猴的专业知识。此外，CNPRC的基础设施和工作人员提供受感染动物的临床分析;这包括物理诊断、微生物分析和血液学评估。兽医病理学家进行全面的尸检和病理分析，并收集组织和器官的所有项目在这个程序。CNPRC已经在SIV/猕猴和RT-SHIV/猕猴系统中进行了几项抗逆转录病毒药物研究;因此，该核心建立在已证明的优势之上 与计划项目的目标直接相关。对于核心B的研究，我们假设SIV/SHIV感染的猕猴模型可用于定义病毒储库、分析潜伏期和研究体内病毒活化。三个具体目的解决了这一假设：目的1：定义SIV/猕猴和RT-SHIV/猕猴系统中的条件，以分析在感染HIV的人中观察到的病毒潜伏期/储库;目的2：分析接受抗逆转录病毒治疗的感染猕猴中的病毒定位;目的3：确定病毒和宿主细胞因子在调节病毒潜伏期、持续性和再活化中的作用。

This Program Project conducts a comprehensive analysis of the mechanism(s) of HIV latency and viral reservoirs. In vitro investigations in tissue culture systems (Projects 1, 2, and 3) will be closely coordinated with in vivo studies in this core ("Non-human Primates for HIV/SIV Reservoirs and Latency"). Accordingly, this core will provide rhesus macaques and appropriate infrastructure support required for the animal model studies in this Program Project. This Core uses macaques housed at the California National Primate Research Center (CNPRC) at UC Davis. This Center is accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC) and includes full-time, licensed veterinarians. Appropriate facilities and expertise are available for the care and handling of macaques inoculated with SIV/SHIV at biosafety levels 2 and 3 (BSL-2, -3). In addition, the CNPRC infrastructure and staff provide for clinical analysis of infected animals; this includes physical diagnosis, microbiological analysis, and hematological assessments. Veterinary pathologists perform comprehensive necropsy and pathology analysis and to collect tissues and organs for all of the projects in this Program. Several studies on antiretroviral drugs, in the SIV/macaque and RT-SHIV/macaque systems, have been conducted at the CNPRC; thus, this Core builds on demonstrated strengths that are directly relevant to the goals of the Program Project. For the studies in Core B, we hypothesize that the macaque model of SIV/SHIV infection can be used to define viral reservoirs, to analyze latency, and to study activation of virus in vivo. Three Specific Aims address this hypothesis: Aim 1: to define conditions in the SIV/macaque and RT-SHIV/macaque systems for analysis of viral latency/reservoirs as observed in humans infected with HIV; Aim 2: to analyze virus localization in infected macaques undergoing antiretroviral therapy; Aim 3: to determine the role of viral and host-cell factors in the regulation of viral latency, persistence, and reactivation.