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 glutathione peroxidase, GSHPx-1. This enzyme represents a major cellular defense mechanism against toxicity associated with reactive oxygen species (ROS). T cells engineered to produce elevated GSHPx-1 activity displayed 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 attenuation of viral replication in Sup-T1 cells. Similarly, exposure of human peripheral blood lymphocytes (PBLs) to low, nontoxic levels of BSO resulted in an approximately 80% decline in HIV-1 replication as indicated by Western blot analysis of viral proteins.