Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.
We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.
Harakeh
S
S
Viral Carcinogenesis, Laboratory, Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.
Jariwalla
R J
RJ
Pauling
L
L
D000998:Antiviral Agents; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D014176:Protein Biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012194:RNA-Directed DNA Polymerase; D001205:Ascorbic Acid