Resveratrol Inhibition of Human Rhinovirus Replication

Resveratrol, a polyphenolic natural product, shows protective properties against several viral infections. Rhinoviruses are the major etiological agents of common cold and asthma exacerbations, however no specific antiviral therapy is available. We evaluated the antiviral effect of resveratrol towards human rhinovirus 16 (HRV-16) in two different cellular models: cell culture monolayer and human nasal epithelium, composed by basal, ciliated and mucus cells. Infection was performed under single cycle or multiple cycles of virus replication conditions. Viral yield in the presence of different non cythopatic concentrations of resveratrol was assessed by plaque assay. Resveratrol was tested on different experimental conditions by measuring its ability 1) to prevent virus infection after pre-treatment of cells or virus, 2) to inhibit early steps of virus multiplication and 3) to reduce virus yield when present during viral replication. Resveratrol showed a strong inhibitory effect on HRV-16 infective particles production in both cellular systems. The inhibition appeared to be dose- and time-dependent. It has been reported that HRV-16 induces activation of NF-kB, which in turn promotes the transcription of ICAM-1, the major receptor for HRV. We examined the effect of resveratrol on the HRV-16-induced expression of ICAM-1 by western blot and direct immuno-fluorescence assay. Resveratrol treatment inhibited the HRV-16-induced increase of ICAM-1 level. Besides, since HRV-16 replication in epithelial cells induces the production of pro-inflammatory cytokines, we evaluated the effects of resveratrol on IL-6, IL-8, RANTES and INF-β levels in human nasal epithelia by ELISA assay. The results of this study suggest that resveratrol may have a possible clinical application in the treatment of HRV infections.