The Flavonoid, Quercetin, Inhibits HIV-1 Infection in Normal Peripheral Blood Mononuclear Cells
Madhavan P.N. Nair, Zainulabedin M. Saiyed, Nimisha H. Gandhi and C. N. Ramchand
DOI : 10.3844/ajidsp.2009.135.141
American Journal of Infectious Diseases
Volume 5, Issue 2
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.
© 2009 Madhavan P.N. Nair, Zainulabedin M. Saiyed, Nimisha H. Gandhi and C. N. Ramchand. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.