Summary: We have characterized several new strains of the various HIV subtypes ranging from A-G of group M, isolates of group O and HIV-2. We have also obtained several drug resistant strains of HIV. We are sequencing the regulatory genes tat, nef, vpu and vpr to look for any possible relationships between these sequence s and co-receptor usage. Studies are underway to evaluate the replication of non clade B, O viruses and drug resistant viruses in in vitro cell systems with specific emphasis on their cell trpoism, replication kinetics, chemokine and cytokine usage. We are working with CDC to develop strategies in Cameroon (Africa) to identify new variants and recombinants of HIV and related viruses. These viruses are being investigated for their infectivity, drug susceptibility and pathogenesis in appropriate cell culture systems and animal models. We have examined the impact of HIV variation on apoptosis, chemokine and cytokine production in donor PBLs. We will also examine the role of tat and nef in faciltitating fasL mediated apoptosis in PBLs and 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 are being investigated. The infectivity of different HIV subtypes and variants for dendritic cells and macrophages are being studied.