The studies performed in this study period focused on virus-host interactions in sooty mangabeys that may explain the lack SIV pathogenesis in the natural host and/or contribute to the risk of zoonotic transmission of SIV. These studies included the following (1) Rate of plasma SIV turnover in sooty mangabeys This data indicated that high level viremia in mangabeys is due to rapid production of SIV rather than decreased clearance; (2) Rate of SIV turnover in tissue compartments of sooty mangabeys This data indicated that SIV is present in many tissues of the sooty mangabey and that there is rapid viral turnover in these tissues; (3) Estimation of the rate of cell proliferation SIV infected sooty mangabeys This data indicated that the rate of cell proliferation is higher in sooty mangabeys with higher level viremia, suggesting the hypothesis that preserved cell proliferative capacity, rather than decreased cell destruction, underlying nonpathogenic SIV infection in sooty managabeys; (4) Cloning sooty mangabey cell receptors that may be involved in SIV entry in the natural host We have cloned and expressed two alleles of sooty mangabey CCR5 and determined that one allele can serve as a viral co-receptor; (5) Generation of SIVsmm stocks derived directly from sooty mangabey tissues We generated one stock of SIVsmm by co-culture of mangabey cells from infected and uninfected mangabeys. These stocks will be useful for experimental infections of sooty managbeys as originally proposed. These studies indicate that massive viral and cell turnover is present in sooty mangabeys that are nonpathogenically infected with SIV, and that capacity for host cell regeneration is likely to be preserved in the natural host of SIV, thereby allowing indefinite persistence of viral replication. Our demonstration that """"""""virologic mayhem"""""""" is insufficient to explain lentiviral pathogenesis is likely to focus greater attention on the effects of virus infection on host r egenerative capacity.
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