Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells.
To elucidate the action of vitamin C on pathogenic human retroviruses, we investigated and compared the effects of noncytoxic concentrations of ascorbic acid (AA), its calcium salt (Ca-ascorbate), and two thiol-based reducing agents [glutathione (GSH) and N-acetyl-L-cysteine (NAC)] against human immunodeficiency virus (HIV)-1 replication in chronically infected T lymphocytes. Ca-ascorbate reduced extracellular HIV reverse transcriptase (RT) activity by about the same magnitude as the equivalent dose of AA. Long-term experiments showed that continuous presence of ascorbate was necessary for HIV suppression. NAC (10 mmol/L) caused less than twofold inhibition of HIV RT and conferred a synergistic effect (approximately eightfold inhibition) when tested simultaneously with AA (0.426 mmol/L). In contrast, nonesterified GSH (less than or equal to 1.838 mmol/L) had no effect on RT concentrations and did not potentiate the anti-HIV effect of AA. These results further support the potent antiviral activity of ascorbate and suggest its therapeutic value in controlling HIV infection in combination with thiols.
Harakeh
S
S
Viral Carcinogenesis Laboratory, Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.
Jariwalla
R J
RJ
D000111:Acetylcysteine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D012194:RNA-Directed DNA Polymerase; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine