IDENTIFYING THE MAJOR TISSUE RESERVOIRS IN SIV/SHIV INFECTED MACAQUES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 通过目前使用的抗逆转录病毒治疗方案不能从感染者身上根除艾滋病毒-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HIV致病机制和疫苗效力的有用模型。我们使用这个模型来探索病毒库在猕猴体内控制病毒复制的可能作用，以及那些血浆中持续存在高病毒血症的猕猴。组织中活跃复制病毒的存在与血浆病毒载量有关。同样，在血浆病毒载量较高的猕猴中也检测到了更多潜伏感染的细胞。发现淋巴是病毒的主要组织储存库，其次是脾和肠道组织。SIV脑炎猕猴脑组织和胸腺中可检测到持续感染细胞。因此，抗逆转录病毒治疗的设计应该是这样一种方式，它可以针对次级淋巴器官中的感染细胞，并减少潜伏和持续感染细胞的产生。T辅助细胞和巨噬细胞是持续和潜伏感染细胞的主要细胞，因此应专门设计疫苗或抗逆转录病毒治疗来保护这些细胞。

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.