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.
Sandstrom
P A
PA
HIV/Retrovirus Disease Branch, Division of AIDS, STD and TB Laboratory Research, National Center for Infectious Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Murray
J
J
Folks
T M
TM
Diamond
A M
AM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014162:Transfection
D000975:Antioxidants; D001555:Benzene Derivatives; D019328:Buthionine Sulfoximine; D005979:Glutathione Peroxidase; D005978:Glutathione; C007164:cumene hydroperoxide