LONGITUDINAL FOLLOW UP OF SIVMAC PATHOGENESIS IN MACAQUES OF CHINESE ORIGIN

这个子项目是众多研究子项目之一

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. We have tested the dynamics of memory CD4+CCR5+ cells (target cells) in GALT in 12 SIV infected Chinese-origin rhesus macaques. Expression of T cell, naive and memory markers were measured by flow cytometry. Eight of 12 monkeys developed AIDS between 6 to 25 months after infection (progressors); 4 were long term nonprogressors (LTNPs) and remained healthy with undetectable plasma viral loads. Memory CD4+ CCR5+ cells were profoundly depleted during acute infection in all 12 monkeys. In progressors, all lacked the ability to maintain restoration of target cells. In the LTNPs, variable memory cell recovery began at day 60 PI and all had restored ¿ 15% of baseline levels by day 180 and maintained this level or increased it. In vivo CD8+ depletion in 2 LNTPs resulted in one to develop AIDS (V542) and the other (AJ07) remains healthy. Our results indicated that profound depletion of target cells in GALT was indistinguishable between progressors and LTNPs in the acute infection. Restoration of target cells during the chronic phase predicted LTNP. Sufficient CD8+ T cells are essential for controlling SIV infection in GALT and required for restoration of target cells. Moreover, host genetic protective factors such as immunogenetics was further studied by analyzing MHC class I alleles, more than 10 new MHC class I locus A and locus B alleles were identified from 9 Chinese-origin rhesus macaques with 48-190 clones per animal. However, when compared progressors with LTNPs, no association of disease progression was found with any particular MHC class I alleles. One recently published paper also indicated that control of simian immunodeficiency virus SIVmac239 is not predicted by inheritance of Mamu-B*17-containing haplotypes by David O'connor's group in the University of Wisconsin (Journal of Virology 2007406-410). Mamu-B*17 was previously recognized as an allele that associated with viral suppression and slow progression.