SUSCEPTIBILITY OF DENDRITIC CELLS TO HIV-1 INFECTION IN-VITRO

We review recent work on the extent of HIV-1 infection of dendritic cells (DCs) and the consequences of exposure to virus. The reported levels of infection of DCs from blood have varied from ''explosive'' to ''undetectable' The only study that used sorted DCs demonstrated little if any infectability, which may not be surprising given the very low levels of CD4 on the populations that were studied. HIV-1-pulsed, highly purified DCs function as potent antigen-presenting cells during the mixed leukocyte reaction and responses to superantigens. At the same time that the HIV-1-pulsed DCs stimulate CD4(+) T cells in DC-T clusters, the virus is transferred to the responding lymphocytes and a vigorous productive infection of the T cells takes place. This pool of transferable HIV-1 is short lived in cultured human blood DCs and likely reflects the capacity of these cells to internalize and recycle vesicles in the endocytic pathway, as revealed with experiments using 0.1-mu m fluorescent latex beads. Current efforts are directed to analyzing the interaction of HIV-1 with several populations of DCs that express higher levels of CD4(+). These include DCs studied in fresh, uncultured blood, as well as skin, thymus, and tonsil DCs. In each case, entry and reverse transcription of HIV-1 are seen, but again, coculture with T cells is required for a productive infection to take place. We conclude that DCs could play a critical role in the pathogenesis of HIV-1 infection, but that the interaction with CD4(+) T cells is a critical variable in analyzing the extent of productive infection and its consequences.