Core - Animal Model

本课题对艾滋病病毒潜伏和病毒传播的机制(S)进行了全面的分析 水库。组织培养系统的体外研究(项目1、2和3)将密切协调。 核心B的活体研究(“非人类灵长类动物的艾滋病毒/SIV储存库和潜伏期”)。因此， 核心B将提供恒河猴和动物模型所需的适当基础设施支持 该计划项目中的学习。这个核心使用的是加州国家灵长类动物研究中心的猕猴 加州大学戴维斯分校的中心(CNPRC)。该中心获得了美国认证协会的认可 实验室动物护理(AAALAC)，包括全职、有执照的兽医。适当的设施和 对于接种SIV/SIV的2级生物安全级别的猕猴的护理和处理有专门知识 和3(BSL-2，-3)。此外，CNPRC的基础设施和工作人员提供感染的临床分析 动物；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，收集所有人的组织和器官 该计划中的项目。SIV/猕猴和RTSHIV/中抗逆转录病毒药物的几项研究 猕猴系统，已在中国人民解放军进行；因此，这一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的项目。对于核心B中的研究，我们假设 SIV/SIV感染的猕猴模型可用于确定病毒库、分析潜伏期和 研究病毒在体内的激活情况。三个具体目标解决了这一假设：目标1：在 SIV/Macaque和RT-Shiv/Macaque系统用于病毒潜伏/储存分析 人类感染艾滋病毒；目标2：分析感染艾滋病毒的猕猴体内病毒的定位 治疗；目标3：确定病毒和宿主细胞因素在调节病毒潜伏期中的作用， 持久化和重新激活。

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 Core B ("Non-human Primates for HIV/SIV Reservoirs and Latency"). Accordingly, Core B 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 RTSHIV/ 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.