Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-κB signaling pathway.

Li Zhang,Weifeng Shi,Jing Sun,Lirong Zhang,Yuyue Wang,Xiaopeng Xu,Yuanyuan Li,Mei Shi,Zhiwen Gu,Yun Ji,Jingtin Jiang

doi:10.1371/journal.pone.0116879

Abstract

Polydatin and resveratrol, as major active components in Polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions. However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71) have not been reported. In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect. Neither polydatin nor resveratrol exhibited influence on viral attachment. Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKβ, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively. Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD) cells could be blocked by resveratrol. These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway. Thus, resveratrol may have potent antiviral effect on EV71 infection.

Highlights

Hand, foot, and mouth disease (HFMD), as a commensal disease, often occurs in children under the age of 10, and can be observed in adolescents and adults on occasion
In order to clarify whether polydatin and resveratrol can inhibit enterovirus 71 (EV71) replication, we have examined the cytotoxicity of resveratrol and polydatin on RD cells and evaluated their treatment efficacy on EV71 infection
To understand whether the inhibitory activity of polydatin and resveratrol on EV71 replication is associated with cytotoxicity, the viability of RD cells subjected to the treatment of polydatin, resveratrol or ribavirin for 2 days was determined

Summary

Introduction

Foot, and mouth disease (HFMD), as a commensal disease, often occurs in children under the age of 10, and can be observed in adolescents and adults on occasion. The common pathogens of HFMD are EV71 and coxsackievirus A16 (CA16). EV71 belongs to the Picornaviridae family, and is characterized by a single-stranded positive RNA genome. Compared with CA16, EV71 often causes aseptic meningitis, encephalomyelitis, and acute flaccid paralysis, and even death [1, 2]. Viruses can only survive in host cells, so it is difficult to develop effective drugs against viruses without the damage on host cells. Several kinds of drugs including interferons, antiviral chemicals, and vaccines have been developed to treat EV71 infection. The treatment efficacy of these developed drugs for EV71 infection is still not confirmed yet [3]

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Conclusion