ANTIOXIDANT DEFENSES INFLUENCE HIV-1 REPLICATION AND ASSOCIATED CYTOPATHIC EFFECTS

HIV-infected cells often exhibit reduced levels of antioxidant enzymes and thiols. To investigate the role of cellular antioxidant defenses in the progression of an acutely spreading HIV-1 infection, human Sup- T1 T cells were engineered to overexpress the selenium-dependent gluta thione peroxidase, GSHPx-1. This enzyme represents a major cellular de fense mechanism against toxicity associated with reactive oxygen speci es (ROS). T cells engineered to produce elevated GSHPx-1 activity disp layed accelerated viral replication and associated cytopathic effects compared to control cells. Conversely, the inhibition of the synthesis of glutathione with buthione sulfoximine (BSO) resulted in the attenu ation of viral replication in Sup-T1 cells. Similarly, exposure of hum an peripheral blood lymphocytes (PBLs) to low, nontoxic levels of BSO resulted in an approximately 80% decline in HIV-1 replication as indic ated by Western blot analysis of viral proteins. (C) 1998 Elsevier Sci ence.