This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In the absence of treatment, infection of rhesus macaques with pathogenic SIV, like HIV infection of humans, is almost always progressive with deterioration of immune function, and ultimately death due to either direct consequences of SIV itself or opportunistic infection. The tempo of progression, however, varies considerably from host to host, even with cloned virus, suggesting that host factors play a role in supporting and/or mitigating the extent and consequences of viral replication. Recent documentation of massive, systemic depletion of SIV 'target' cells (CCR5+, CD4+ memory T cells) in early SIVmac239 infection, and a concomitant, profound increase in the production and turnover of this population suggests that target cell availability and mechanisms of target cell generation may significantly contribute to the outcome of infection. Indeed, our preliminary data suggest that plateau-phase viral replication may be largely supported by infection of 'new' T cell targets generated by this marked increase CD4+ memory T cell turnover. The overall goal of this project is therefore to characterize the nature and regulation of T cell turnover in various stages of SIV infection, and to ascertain the impact of this regulation on viral dynamics and disease progression.
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