IMMUNE RESTORATION AND PROTECTION IN SIV-INFECTED LONG TERM NONPROGRESSORS

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. The objective of this project is to explore the mechanisms of virus control and immune protection in SIVmac-infected long term nonprogressors (LTNP) of Chinese-origin rhesus macaques (Ch Rh) by retrospective study and also prospective monitoring of 7 SIVmac239-infected Ch Rh. We hypothesize that comparison of immune responses between progressors and LTNP within the same subtype of rhesus macaques will yield information, which can be directly applied to vaccine and therapeutic strategies to combat HIV-1 infection. We will test 3 specific aims, 1): To compare functional virus-specific and innate immune responses in both mucosal and systemic lymphoid tissues of SIV-infected progressing, and LTNP Ch Rh macaques. Polychromatic intracellular cytokine staining for virus-specific T cell responses, and virus specific antibody responses will be compared in blood, lymph node, and intestines of progressors and LTNP. 2): To examine and compare gene regulation in mucosal and systemic lymphoid tissues of progressing and LTNP Ch Rh macaques infected with SIV. Rhesus specific Affymetrix gene array chips will be applied to examining mucosal and systemic tissues of progressing and LTNP macaques. We hypothesize that specific patterns of gene regulation will correlate with LTNP. 3): To examine virologic factors in LTNP and progressors. Conceivably, LTNP may result from the emergence/dominance of "unfit" or mutant viruses rather than host immune responses. Thus, viruses will be isolated by cell culture from LTNP at acute peak viremia and during the maximal virus suppression period. We will compare virus fitness of the two isolates in vitro, we will also examine viral sequences and analysis mutations. This will test a hypothesis that host-specific immune mechanisms rather than viral factors are responsible for the LTNP state.