The Flavonoid, Quercetin, Inhibits HIV-1 Infection in Normal Peripheral Blood Mononuclear Cells

Abstract

Problem statement: Flavonoids and related polyphenols, have been known to possess cardioprotective, anti-tumor, anti-inflammatory, anti-allergic and anti-viral activities. Previous studies have shown that flavonoid, quercetin significantly downregulates expression of pro-inflammatory cytokines in cultured cells via modulation of NFκB and p38MAPK signaling pathways. In the current study, we hypothesize that quercetin exerts anti-HIV activity by differential modulation of pro-and anti-inflammatory cytokine expression in normal PBMCs. Approach: Cultures of PBMC received either different concentrations of quercetin (1-50 μM) or media alone. The anti-HIV effects of quercetin was evaluated in an in vitro infection model by quantitaing the HIV-1 LTR gene suppression by quantitative Real Time PCR, HIV-1 p24 antigen production by ELISA and viral infectivity by MAGI cell assay. Results: Our results showed that quercetin significantly downregulates p24 antigen production, LTR gene expression and viral infectivity in a dose dependent manner (5-50 mM) as compared to HIV infected untreated control PBMCs. Further, we reported that quercetin significantly downregulated the expression of the pro-inflammatory cytokine, TNF-α with concomitant upregulation of anti-inflammatory cytokine IL-13 as determined by measurement of gene expression and protein production. A higher level of IL-13 is known to inhibit TNF-a production and also HIV-1 infection. Thus, differential modulation of pro-and anti-inflammatory cytokines could be one of the possible mechanisms for the anti-HIV effects of quercetin. Conclusion: Better understanding of the mechanisms underlying the anti-HIV effects of quercetin may help to develop a new neutraceutical agent useful in the treatment of HIV-1 infected subjects in conjunction with conventional therapeutic regimens.