Potent inhibition of human enterovirus 71 replication by type I interferon subtypes

Background: Enterovirus 71 (EV71) infection can induce a series of syndromes including herpangina, viraemia, hand-foot-and-mouth disease and even death. Outbreaks of EV71 infection have been reported periodically over the world and have caused a great number of casualties and a high medical expenditure. Some interferons (IFNs) have been used for the treatment of viral infections for decades; however, conventional IFNs only display mild anti-EV71 activities. No effective drug is currently available for the treatment of EV71 infection. Here, we aimed to investigate whether some IFN subtypes display potent anti-EV71 activities. Methods: The antiviral activities of 17 type I IFNs were assayed in Vero cells using the cytopathic effect method. Cells were incubated with different concentrations of type I IFNs before or after virus infection. Viral replication was determined by quantitative real-time PCR (qRT-PCR). The expression levels of IFN downstream antiviral genes were also measured by qRT-PCR. Results: Out of 17 type I IFNs, 4 IFNs (IFN-alpha 4, IFN-alpha 6, IFN-alpha 14 and IFN-alpha 16) displayed potent antiviral activity. Compared with conventional IFN-alpha 2a, IFN-alpha 14 displayed approximately 20x higher antiviral activity. The superior antiviral effect of IFN-alpha 14 was caused by a strong induction of the downstream antiviral effectors. Conclusions: IFN-alpha 14 and three other IFNs could be considered for the treatment of EV71 infection.