IDENTIFYING THE MAJOR TISSUE RESERVOIRS IN SIV/SHIV INFECTED MACAQUES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 通过目前使用的抗逆转录病毒治疗方案无法从受感染个体中根除HIV-1。在感染早期建立的病毒库在很长一段时间内不受抗逆转录病毒治疗的影响，并且能够在治疗中断时补充全身感染。猴免疫缺陷病毒-恒河猴艾滋病模型是研究艾滋病发病机制和疫苗效果的有效模型。我们已经使用这个模型来探索猕猴中控制病毒复制的病毒储库与那些在血浆中具有持续高病毒血症的猕猴的可能作用。组织中活跃复制病毒的存在与血浆病毒载量相关。类似地，在具有高血浆病毒载量的猕猴中检测到更潜伏感染的细胞。发现淋巴结是病毒的主要组织储存库，其次是脾和肠组织。猴SIV脑炎脑和胸腺中检测到持续感染细胞。因此，抗逆转录病毒治疗的设计应使其能够靶向次级淋巴器官中的感染细胞，并减少潜伏性和持续性感染细胞的产生。辅助性T细胞和巨噬细胞被发现是携带持续和潜伏感染细胞的主要细胞，因此疫苗或抗逆转录病毒疗法应该专门设计来保护这些细胞。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eradication of HIV-1 from an infected individual cannot be achieved by current usage of antiretroviral therapy regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time and are able to replenish systemic infection upon interruption of the treatment. Simian immune deficiency virus-rhesus macaque models of AIDS are a useful model for studying HIV pathogenesis and vaccine efficacy. We have used this model to explore the possible role of viral reservoirs in macaques that control viral replication with those that have persistently high viremia in plasma. The existence of actively replicating viruses in tissues correlates with plasma viral load. Similarly more latently infected cells were detected in macaques with a high plasma viral load. Lymph nodes were found to be the major tissue reservoir of virus followed by spleen, and intestinal tissues. Persistently infected cells in brain and thymus were detected in macaques with SIV-encephalitis. Therefore, anti-retroviral therapy should be designed in such a way that it can target infected cells in secondary lymphoid organs and reduce the generation of latently and persistently infected cells. T helper cells and macrophages were found to be the major cells that harbor persistently and latently infected cells, thus a vaccine or antiretroviral therapy should be specifically designed to protect these cells.