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 association between CD4+ T-cell depletion and an accelerated rate of disease progression is well established for HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques. However, SIV infection in its natural primate host (i.e. sooty mangabeys) results in near normal levels of CD4+ T-cells despite similar plasma viral loads. Recent evidence suggests that the absence of clinical symptoms in SIVsmm+ mangabeys corresponds with a lack of T cell activation and bystander apoptosis. Following transfer of plasma from an SIV+ mangabey in the Yerkes colony, two mangabeys exhibited a decline in CD4+ T cell levels to below 100 cells/ul of blood which is also be observed in lymph nodes. These levels have remained between 18 and 100 cells/ul of blood for the past 7 years. The presence of AIDS defining CD4+ T-cell levels in SIV+ mangabeys is an uncommon occurrence within the Yerkes colony (only four of the 105 SIV+ mangabeys screened are CD4-low). The goal of these experiments is to characterize the mechanisms behind the observation of CD4 depletion in the absence of activation induced apoptosis in these SIVsmm-passaged mangabeys.During the reporting period, three additional mangabeys were infected with plasma virus from a CD4-low mangabey. The CD4 levels in these three mangabeys declined to below 100 CD4 cells/ul of blood by 21 days post-infection and have remained at these low levels through to the current timepoint (80 days post-infection). These data indicate that the virus itself is responsible for the dramatic decline in CD4 levels, indicating that viral cytopathicity is not sufficient to induce clinical signs of AIDS in natural monkey SIV host species. These three newly infected mangabeys and 2 previously identified CD4-low mangabeys are still being followed to characterize the immunologic changes that are occurring.
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