Mechanistic aspects of ascorbate inhibition of human immunodeficiency virus.
We have investigated the molecular basis of the inhibitory effect of ascorbate (vitamin C) on human immunodeficiency virus (HIV) expression in unstimulated chronically infected and reporter cell lines. Comparison of intracellular HIV RNA and protein patterns of ascorbate-treated cells with corresponding patterns of untreated controls, did not show significant differences in the synthesis or processing of individual viral RNA and polypeptides, indicating that the inhibitory effect of ascorbate is not directed at steps of viral transcription or translation. Enzyme assays on cell extracts showed that the activity of an HIV LTR-directed reporter protein made in ascorbate-treated cells was reduced to approximately 11% relative to that of untreated control. These results, combined with previous observations on the suppression of HIV RT activity, are consistent with a mechanism of action in which ascorbate exerts a posttranslational inhibitory effect on HIV by causing impairment of enzymatic activity.
Harakeh
S
S
Viral Carcinogenesis and Immunology Program, Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.
Niedzwiecki
A
A
Jariwalla
R J
RJ
D001205:Ascorbic Acid / Q000494:pharmacology*; D015152:Blotting, Northern; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017930:Genes, Reporter; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000096:biosynthesis; D018894:Reverse Transcriptase Inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000096:biosynthesis
D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D001616:beta-Galactosidase; D001205:Ascorbic Acid