Suppression of human immunodeficiency virus
replication by ascorbate in chronically and acutely infected cells.
Proc Natl Acad Sci U S A 1990 Sep;87(18):7245-9 (ISSN: 0027-8424)
Harakeh S; Jariwalla RJ; Pauling LViral Carcinogenesis, Laboratory,
Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.
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.