The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells

Quercetin is a major component of the plant Glycyrrhiza uralensis, which is largely used as a traditional medicine in Asia. Quercetin has been reported to have several biological activities, which include anti-viral and anti-inflammatory effects. We explored the molecular mechanism linking anti-viral and anti-inflammatory activities using an in vitro herpes simplex virus-1 (HSV-1) infection model. Raw 264.7 cells were infected with HSV-1 in the presence or absence of different concentrations of quercetin and infected cell lysates were harvested 24 h later. HSV plaque reduction assays, western blotting (HSV-1gD, HSV-1 ICP0, TLR-2, 3, 9, NF-κB, IRF3), and real time PCR (HSV-1ICP0, HSV-1UL13, HSV-1UL52) were performed to elucidate the mechanism responsible for the anti-HSV-1 effect of quercetin. In addition, TNF-α level was measured. Quercetin significantly lowered HSV infectivity in Raw 264.7 cells and inhibited the expressions of HSV proteins (gD, ICP0) and genes (ICP0, UL13, UL52). Interestingly, quercetin specifically suppressed the expression of TLR-3, and this led to the inhibitions of inflammatory transcriptional factors (NF-κB and IRF3). These findings suggest that the anti-HSV-1 effects of quercetin are related to the suppression of TLR-3 dependent inflammatory responses in Raw 264.7 cells.