The applicant proposes to investigate the infection of primary peripheral dendritic cells by HIV. He will attempt to investigate early events in HIV replication in dendritic cells, including the process and kinetics of reverse transcription and integration. The role of HIV regulatory genes in replication in these cells will also be examined. The investigator proposes replication studies on isogenic strains of HIV which are defective in one of the regulatory genes, including tat (transactivator), rev (regulator of virion protein expression [formerly art/trs]), vif (virion infectivity factor [formerly SOR]), vpr (function unknown), vpu (function unknown), and nef (negative regulatory factor [formerly 3' ORF]). Replication of virus with a defect in a regulatory protein will be compared to replication of the parental virus in the dendritic cell population and the ability of fresh HIV isolates to infect these cells will also be investigated. Since HIV-infected dendritic cells have been isolated from infected patients, this indicates that natural as well as laboratory isolates can infect this cell type. The ability of natural isolates to infect fresh dendritic cell populations will be compared to that of laboratory strains and the transfer of virus infection from infected dendritic cells to primary CD4 T cell populations will also be examined. Preliminary experiments indicate that transfer of infection of T cell clones propagated in the presence of dendritic cells does not result in the death of either the dendritic cells or the CD4+ T cells. The applicant proposes to investigate further this unusual means of T cell infection.
