HIV-1 Tat protects CD4(+) Jurkat T lymphoblastoid cells from apoptosis mediated by TNF-related apoptosis-inducing ligand

We have here investigated the effect of TNF-related apoptosis-inducing liga nd (TRAIL), a new member of the TNF cytokine superfamily, on the survival o f Jurkat lymphoblastoid cell lines stably transfected with plasmids express ing the wild-type or mutated (Cys22) human immunodeficiency virus type 1 (H IV-1) tot gene. Jurkat cells transfected with wild-type tot were resistant to TRAIL-mediated apoptosis, while Jurkat cells mock-transfected with the c ontrol plasmid or with a mutated nonfunctional tat cDNA were highly suscept ible to TRAIL-mediated apoptosis. Also, pretreatment with low concentration s (10-100 ng/ml) of extracellular synthetic Tat protein partially protected Jurkat cells from TRAIL-mediated apoptosis. Taken together, these results demonstrated that endogenously expressed tat and, to a lesser extent, extra cellular Tat block TRAIL-mediated apoptosis. Since it has been shown that p rimary lymphoid T cells purified from HIV-1-infected individuals are more s usceptible than those purified from normal individuals to TRAIL-mediated ap optosis, our findings underscore a potentially important role of Tat in pro tecting HIV-1-infected cells from TRAIL-mediated apoptosis. (C) 2001 Academ ic Press.