HIV-1 UP-REGULATES FAS LIGAND EXPRESSION IN CD4(-CELLS IN-VITRO AND IN-VIVO - ASSOCIATION WITH FAS-MEDIATED APOPTOSIS AND MODULATION BY AURINTRICARBOXYLIC ACID() T)

CD4(+) T-lymphocyte apoptosis has been associated with human immunodef iciency virus (HIV)-1 infection in vitro, paralleling the expression o f Fas (APO-1, CD95) on peripheral blood mononuclear cells from patient s with HIV disease. However, the link between Fas induction, T-cell ac tivation, and cell death is unclear. We document, for the first time, marked upregulation of expression of mRNA for the ligand for Fas in pe ripheral blood mononuclear cells from HIV seropositive individuals, an d demonstrate the ability of HIV infection to induce such expression i n CD4(+) T cells in vitro. We also define the relevance of this expres sion to HIV-mediated CD4(+) T cell death. Our ability to downregulate Fas ligand message and suppress HIV-mediated apoptosis with aurintrica rboxylic acid, a clinically used protease inhibitor with known activit y against programmed cell death in other systems, may open up a new ar ea of therapy for HIV infection.