LIPID HYDROPEROXIDES INDUCE APOPTOSIS IN T-CELLS DISPLAYING A HIV-ASSOCIATED GLUTATHIONE-PEROXIDASE DEFICIENCY

8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell line, which we have previously shown to be extremely susceptib le to hydrogen peroxide (H2O2)-induced apoptosis due to a HIV-associat ed catalase deficiency. Here we report that HIV gene expression additi onally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing b y 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several o ther hydroperoxy fatty acids. Whereas the viability of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 muM 15-HPETE, simila rly treated 8E5 cells underwent apoptosis, as demonstrated by morpholo gical changes and the presence of fragmented DNA. The unique susceptib ility of 8E5 cells was attributable to their inability to convert 15-H PETE to 15-hydroxyeicosatetraenoic acid (15-HETE) owing to a marked re duction in glutathione peroxidase activity. Since oxidized lipids have been reported to accumulate in oxidatively stressed, HIV-infected ind ividuals, a HIV-associated glutathione peroxidase deficiency may contr ibute to the depletion of CD4 T cells that occurs in the acquired immu ne deficiency syndrome (AIDS).