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.The predictive value of acute GALT CD4+ T-cell depletion in lentiviral infections was assessed by comparing three animal models illustrative of the outcomes of SIV infection: pathogenic infection (SIVsmm infection of rhesus macaques-Rh), persistent non-progressive infection (SIVagm infection of African green monkeys-AGMs) and transient, controlled infection (SIVagm infection of Rh). Massive acute depletion of GALT CD4+ T-cells was a common feature of acute SIV infection in all three models. The outcome of infection, however, differed substantially between the three models: in SIVsmm-infected Rh, the acute GALT CD4+ T-cell depletion was persistent and continued with disease progression; in AGMs, intestinal CD4+ T-cells were restored during chronic infection in the context of normal levels of apoptosis and immune activation, absence of damage to the mucosal barrier and an anti-inflammatory environment established early in infection; in SIVagm-infected Rh, complete control of viral replication resulted in restoration of the mucosal barrier and immune restoration. Therefore, our data support a revised paradigm wherein severe GALT CD4+ T-cell depletion during acute pathogenic HIV and SIV infections of humans and Rh is necessary but neither sufficient nor predictive of disease progression, with levels of immune activation, proliferation and apoptosis being key factors involved in determining progression to AIDS.
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