Abstract

There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.

Highlights

  • Enterovirus 71 (EV71), a member of the Picornaviridae family, is a non-enveloped singlestranded RNA virus

  • When the cells were pretreated with 15 μM of Oblongifolin M (OM) 4 hours prior to EV71 infection, most cells were healthy with only a few exhibiting cytopathic effects (CPE) (Figure 1C), an indication that the infected cells were significantly protected from CPE

  • We showed that OM did not affect the ratio of Firefly luciferase (FLuc)/ Renilla luciferase (RLuc) when cells were transfected with pRF plasmid; the ratio of FLuc/RLuc decreased after cells were transfected with pIRES and treated with OM

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Summary

Introduction

Enterovirus 71 (EV71), a member of the Picornaviridae family, is a non-enveloped singlestranded RNA virus. It is the major causative agent of repeated outbreaks of hand, foot and mouth disease (HFMD) [1, 2]. Especially those among in infants and children, EV71 infection causes severe neurological complications such as aseptic meningitis, brain stem encephalitis, pulmonary edema, poliomyelitislike paralysis and eventual death. The continuous outbreaks of EV71 in Asia-Pacific region have caused considerable deaths [3]. HFMD cases were reported in China between 2008 and 2012, of which 2457 were fatal [4, 5]. No effective antiviral drug is currently used for treating EV71 infection [6]; there is an urgent need for effective agent against EV71 infection

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