HIV-1 upregulates Fas ligand expression in CD4(+) T cells in vitro and in vivo: Association with Fas-mediated apoptosis and modulation by aurintricarboxylic acid

CD4(+) T-lymphocyte apoptosis has been associated with human immunodeficiency virus (HIV)-1 infection in vitro, paralleling the expression of Fas (APO-1, CD95) on peripheral blood mononuclear cells from patients with HIV disease. However, the link between Fas induction, T-cell activation, and cell death is unclear. We document, for the first time, marked upregulation of expression of mRNA for the ligand for Fas in peripheral blood mononuclear cells from HIV seropositive individuals, and demonstrate the ability of HIV infection to induce such expression in CD4(+) T cells in vitro. We also define the relevance of this expression to HIV-mediated CD4(+) T cell death. Our ability to downregulate Fas ligand message and suppress HIV-mediated apoptosis with aurintricarboxylic acid, a clinically used protease inhibitor with known activity against programmed cell death in other systems, may open up a new area of therapy for HIV infection.