Our laboratory has isolated virus from a few non progressors and progressors and performed sequence analysis of the viral regulatory and env genes. The tropism of virus from these individuals has been studied. Results indicate that these viruses can replicate in PBMCs but not in some cell lines of T cell and monocytic origin. The role of certain cytokines and chemokines including co-receptor usage in the establishment of the non progressive phenotype has been investigated. Similar studies are underway to evaluate the replication of non clade B and HIV-1 Group O viruses and drug resistant viruses in in vitro cell systems. We have initiated studies to identify new variants and recombinants of HIV and related viruses. These viruses will be investigated for their infectivity, drug susceptibility and pathogenesis in appropriate cell culture systems and animal models. We will also examine the role of tat and nef in faciltitating fasL mediated apoptosis in dendritic cells. These studies will be also carried out in SCID mice. Effects of tat and nef on the regulation of chemokines in susceptible dendritic cells will also be investigated. The infectivity of different HIV subtypes and variants for dendritic cells and macrophages will also be studied.