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. 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.