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. Sooty mangabeys are a natural host of the simian immunodeficiency virus (SIV) that typically do not develop AIDS despite sustained high viral loads. Understanding the dynamics of T-lymphocyte turnover in these animals may shed light on the mechanisms of CD4+ T cell depletion in HIV-infected humans and SIV-infected rhesus macaques. 6 SIV-infected and 5 uninfected sooty mangabeys were given daily BrdU i.p. for 2 weeks. BrdU incorporation in T-cells was measured frequently during the labeling (first 2 weeks) and the follow-up de-labeling phase (median 10 weeks). The percentage of BrdU labeled T-cells vs time was fitted using a model of T-cell dynamics, from which we estimated the average death rate of the T-cell population. The mean death rate for both uninfected and infected CD4+ T-cells was 0.01 day-1, and for CD8+ T-cells it was 0.008 day-1 and 0.009 day-1, respectively. Using the Mann-Whitney U-test, there was no statistically significant difference in the average death rates of uninfected and infected monkeys, either in the CD4+ (p=0.53) or the CD8+ (p=0.41) T cell subsets. In contrast to hosts with pathogenic sequelae of lentiviral infection, CD4+ and CD8+ T-cell turnover as measured by BrdU incorporation is not increased in SIV-infected sooty mangabeys. This suggests that the natural host and virus have co-evolved so that viral infection does not increase average CD4+ T cell death rates despite ongoing viral replication. Understanding how this equilibrium is achieved may be relevant for HIV infection.
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