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 mechanisms underlying the lack of disease progression in natural SIV hosts are still poorly understood. To test the hypothesis that SIV-infected AGMs avoid AIDS due to virus replication occurring in long-lived infected cells, we infected six animals with SIVagm and treated them with potent antiretroviral therapy [ART: (PMPA, tenofovir) and (FTC, emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 hours after ART initiation. Significant decrease of viral load was observed in PBMCs and intestine. Mathematical modeling of viremia decay post-ART indicates a half-life of productively infected cells ranging from 4 to 9.5 h, i.e., faster than previously reported for HIV and SIV. ART induced a slight but significant increase in peripheral CD4+ T-cell counts but no significant changes in CD4+ T-cell levels in LNs and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation and apoptosis, already low in chronically SIVagm-infected AGMs. Collectively, these results indicate that, in SIVagm-infected AGMs, the bulk of virus replication is sustained by short-lived cells; therefore, differences in disease outcome between SIVmac infection of macaques and SIVagm infection of AGMs are unlikely due to intrinsic differences of the in vivo cytopathicity between the two viruses.
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