VIRAL CYTOPATHICITY IN CD4-LOW SIV PASSAGED MANGABEYS

Emory University, Atlanta GA

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Abstract

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. 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. 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 8 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 was to characterize the mechanisms behind the observation of CD4 depletion as well as assess the ability of these mangabeys to mount immune responses in a CD4-low mileu. To undertake this study, three additional mangabeys were infected with plasma virus from a CD4-low mangabey and the CD4 levels in these three mangabeys declined to below 100 CD4 cells/ul of blood by 21 days post-infection. We recently tested the ability of the now 5 CD4-low SIV+ mangabeys to respond to an influenza vaccination. We vaccinated them twice and sent the plasma to the CDC for analysis to quantify the levels of influenza specific antibodies. In this way we will be able to determine if mangabeys are able to elicit effective immune responses even when their CD4+ T cell levels are low.