Core - Animal Model

该项目对艾滋病毒潜伏期和病毒感染的机制进行了全面分析。 水库将密切协调组织培养系统的体外研究（项目1、2和3） 核心B（“HIV/SIV储库和潜伏期的非人灵长类动物”）中的体内研究。因此，委员会认为， 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 在这个项目的研究。这个核心使用了加州国家灵长类动物研究所的猕猴 中心（CNPRC）在加州大学戴维斯分校。该中心是由美国认证协会认可的， 实验室动物护理（AAALAC），包括全职，持牌兽医。适当的设施和 在生物安全级别2下，可获得护理和处理接种SIV/SHIV的猕猴的专业知识 和3（BSL-2，-3）。此外，CNPRC的基础设施和工作人员为感染者提供临床分析。 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，并收集所有的组织和器官， 这个项目中的项目。在SIV/猕猴和RTSIV/猕猴中进行的几项抗逆转录病毒药物研究 猕猴系统，已在CNPRC进行;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。针对这一假设，有三个具体目标：目标1： 用于分析病毒潜伏期/储库的SIV/猕猴和RT-SHIV/猕猴系统， HIV感染者;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 治疗;目的3：确定病毒和宿主细胞因子在调节病毒潜伏期中的作用， 持久性和再激活。

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.