IDENTIFYING THE MAJOR TISSUE RESERVOIRS IN SIV/SHIV INFECTED MACAQUES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尽管抗逆转录病毒疗法在控制血液中病毒复制方面有效，但它未能从患者中“清除”HIV-1感染，表明存在难治性病毒储库。 显然，血液不是病毒的主要来源，因为几项研究表明，血液中感染细胞的频率极低，即使在持续性血浆病毒血症的患者中也是如此。 一些研究表明，淋巴结（LN）作为HIV感染患者的病毒储存库，与血液相比，在LN中观察到感染细胞的频率确实更高，但在某些个体中，感染细胞在LN中也检测不到，特别是在控制感染的患者中。 这些发现，结合我们的初步数据，表明其他组织作为主要的病毒库，特别是肠道诱导淋巴组织。识别和量化主要储库的相对贡献，并确定长期未进展者和进展为AIDS的患者之间的组织或细胞储库是否存在差异，是设计对抗这些储库的策略的逻辑“第一步”。 这些研究将评估和比较SIV/SHIV感染的主要组织和细胞储库。我们期望这些数据将直接适用于治疗和疫苗研究，因为这些结果可以将这些努力集中在最相关的组织和细胞储库上。目前，我们无法对储库细胞的分布和表型得出明确的结论，但正在取得良好的进展，并有望在规定的时间框架内完成拟议的项目。

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. Despite the effectiveness of antiretroviral therapy in controlling virus replication in blood, it fails to "clear" HIV-1 infection from patients, indicating the existence of a refractory viral reservoir(s). Clearly blood is not the major source of virus as several studies have shown the frequency of infected cells in blood is extremely low, even in patients with persistent plasma viremia. A few studies have demonstrated that lymph nodes (LN) as a viral reservoir in HIV-infected patients, and indeed higher frequencies of infected cells are observed in LN compared to blood, but in some individuals, infected cells are also undetectable in LN, particularly in patients who are controlling infection. These findings, combined with our preliminary data, suggest that other tissues serve as major viral reservoirs, particularly the intestinal inductive lymphoid tissues. Identifying and quantifying the relative contribution of the major reservoirs and determining whether there are differences in tissue or cellular reservoirs between long term nonprogressors and those who progress to AIDS is a logical "first step" for designing strategies to combat these reservoirs. These studies will assess and compare the major tissue and cellular reservoirs for SIV/SHIV infection. We expect these data will be directly applicable to both treatment and vaccine studies, in that these results may focus these efforts towards the most relevant tissue and cellular reservoirs. At present, we cannot draw definitive conclusions on the distribution and phenotype of reservoir cells but are making excellent progress and expect to finish the proposed project within the stipulated time frame.