Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH

•L3HYPDH is induced by IFN-Ι in a cell type-dependent manner.•L3HYPDH inhibits EV71 replication.•L3HYPDH inhibits viral translation by targeting the 5′UTR. Enterovirus 71 (EV71) is the common causative agent of hand-foot-mouth disease (HFMD). Despite evidence in mice model suggested that the interferon (IFN) signaling pathways play a role in defending against this virus, knowledge on the IFN-mediated antiviral response is still limited. Here we identified an IFN-stimulated gene (ISG) called L3HYPDH, whose expression inhibits EV71 replication. Mapping assay indicated that amino acids 61–120 and 295–354 are critical for its optimal antiviral activity. Mechanismly, L3HYPDH specifically inhibits protein translation mediated by EV71 internal ribosome entry site (IRES). Our data thus uncovered a new mechanism utilized by the host cell to restrict EV71 replication.