Basic studies on strategy against HIV

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In this research project, we have obtained the results as summarized below. Our results would contribute much to the understanding of HIV-1 replication and to the development of anti-HIV-1 strategies.(1) Function of HIV-1 Gag. We have demonstrated the presence of Gag mutants, with defect of uncoating/reverse transcription process in the early phase, that replicate in a cell-dependent manner. This result implies that some cell factor (s) is involved in the process. We also have demonstrated the ability of many of the early Gag mutants to inhibit strongly the replication of wild-type virus.(2) HIV-1 Env and cellular factor. We have demonstrated the involvement of a host cell factor (s) in the Env incorporation into HIV-1 virions.(3) Function of HIV-1 Vif. Two HIV-1 Vif mutants, with mutations in the hydrophilic or effector region, have been found to have target cell-dependent replication potentials. These mutants belong to a novel category of the Vif mutants.(4) Function of HIV-1 Nef. We have found that the region of HIV-1 Nef governing MHC-I down-regulation is proximate in the α helix domain but is dissociated functionally from that determining enhancement of viral infectivity in vitro, virion incorporation of Nef, and CD4 down-regulation. This result suggests that HIV-1 Nef is immunologically important in the infected hosts.(5) Function of HIV-1 Vpr. Both cell- and virion-associated HIV-1 Vpr have been found to arrest the cell cycle at the G2/M phase and to induce cell apoptosis. No anti-apoptotic activity of HIV-1 Vpr has been noted.