Micronutrient cooperation in the suppression of HIV production in chronically and latently infected cells

Nutrients are known to display pharmacologic activity against viruses and to exert cooperative effects in cells. To study the influence of nutrient cooperation on HIV production in chronically infected T lymphocytes, we evaluated the individual and combined effects of nutrients on HIV-1 reverse transcriptase (RT) released into the culture supernatant. In unstimulated cells, low concentrations of single nutrients, namely ascorbic acid (AA), green tea polyphenols (GT) or lysine, did not significantly suppress HIV-1 RT production. However, when GT (25 µg/ml) and AA (32-64 µg/ml) were combined and applied to cells, extracellular RT was significantly reduced relative to the control. Combining GT (25 µg/ml) with lysine (25 µg/ml) also reduced the RT level to a greater extent (51% of control) than was observed wih lysine alone, and the addition of AA (16 µg/ml) to the combination further decreased RT to 17% of the control (p=0.06). Under the same assay conditions, the nucleoside analog azidothymidine did not significantly suppress HIV production at low to moderate concentrations (0.5-1.0 µg/ml), but did reduce the RT level to 40% of the control (p=0.02) at the highest dose tested (2 µg/ml). In unstimulated cells as well as in latently infected cells stimulated with mitogen (PMA or TNF-α), a nutrient mixture containing GT, AA and amino acids imparted significantly greater RT suppression than equivalent concentrations of key individual components. Nutrient effects on RT suppression were virus-specific and were not due to non-specific cellular toxicity. These results suggest that relatively non-toxic micronutrient combinations are more potent than single nutrients in suppressing virus production in chronically infected T cells, indicating that the constituent nutrients have a cooperative effect in HIV inhibition.