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。 尽管抗逆转录病毒疗法在控制血液中的病毒复制方面是有效的，但它未能从患者身上“清除”艾滋病毒-1感染，这表明存在一个难治的病毒库(S)。显然，血液不是病毒的主要来源，因为多项研究表明，血液中感染细胞的频率极低，即使是在患有持续性血浆病毒血症的患者中也是如此。一些研究表明，在HIV感染患者中，淋巴结节(LN)是病毒的储存库，确实与血液相比，LN中感染细胞的频率更高，但在一些人中，LN中也检测不到感染细胞，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，表明其他组织是主要的病毒储存库，特别是肠道诱导淋巴组织。确定和量化主要储蓄者的相对贡献，并确定长期无进展的人和进展为艾滋病的人之间在组织或细胞储存物上是否存在差异，是设计抗击这些储存物的战略的合乎逻辑的第一步。 这些研究将评估和比较SIV/SIV感染的主要组织和细胞储存库。我们预计这些数据将直接适用于治疗和疫苗研究，因为这些结果可能会将这些努力集中在最相关的组织和细胞储存库上。目前，我们还不能就储集层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，预计将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.