Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

flavonoids and related polyphenols, in addition to their cardioprotective, anti-tumor, anti-inflammatory, anti-carcinogenic and anti-allergic activities, also possess promising anti-hiv effects. recent studies documented that the ？-chemokine receptors, ccr2b, ccr3 and ccr5, and the a-chemokine receptors, cxcr1, cxcr2 and cxcr4 serve as entry coreceptors for hiv-1. although flavonoids and polyphenolic compounds elicit anti-hiv effects such as inhibition of hiv-1 expression and virus replication, the molecular mechanisms underlying these effects remain to be clearly elucidated. we hypothesize that flavonoids exert their anti-hiv effects, possibly by interfering at the hiv co-receptor level. we investigated the effect of flavonoid constituents of a proprietary grape seed extract (gse) on the expression of hiv-1 coentry receptors by immunocompetent mononuclear leukocytes. our results showed that gse significantly downregulated the expression of the hiv-1 entry co-receptors, ccr2b , ccr3 and ccr5 in normal pbmc in a dose dependent manner. further , gse treated cultures showed significantly lower number of ccr3 positive cells as quantitated by flow cytometry analysis which supports rt-pcr gene expression data.investigations of the mechanisms underlying the anti-hiv-1 effects of grape seed extracts may help to identify promising natural products useful in the prevention and /or amelioration of hiv-1 infection