Abstract
Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV.
Highlights
The hepatitis C virus (HCV) is an enveloped, positive strand RNA virus belonging to the Flaviviridae family[1] with 7 major genotypes[2]
Quercetin significantly decreased the intracellular amount of negative-strand HCV RNA, a hallmark of HCV genome replication, assessed at day 1 post-inoculation (61% ± 5.89% inhibition; p = 0.0084) and day 3 post-inoculation (68.38% ± 10% inhibition; p < 0.001) when compared to Dimethyl sulfoxide (DMSO)-treated infected cells (Fig. 1a,b, respectively)
To further examine the impact of quercetin on the HCV life cycle, we evaluated the extracellular production of the viral particles
Summary
The hepatitis C virus (HCV) is an enveloped, positive strand RNA virus belonging to the Flaviviridae family[1] with 7 major genotypes[2]. The HCV life cycle is tightly linked to the host cell lipid metabolism. The price is still one of the major barriers to achieve hepatitis C eradication mainly in low- and middle-income countries[16]. Several flavonoids such as naringenin and catechin have shown antiviral properties against HCV17. Quercetin has been found to inhibit DGAT activity[26,27], an enzyme involved in the assembly step of the HCV life cycle[12]. The main aims of this study were to further elucidate at which steps of the virus life cycle and by which mechanisms quercetin exerts anti-HCV activity
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