IDENTIFYING THE MAJOR TISSUE RESERVOIRS IN SIV/SHIV INFECTED MACAQUES

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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.