Up-regulation of interferon-stimulated genes (ISGs) is key to antiviral states mediated by interferon (IFN) but little is known about activity and underlying mechanisms of most ISGs against Enterovirus 71 (EV71). EV71 causes hand-foot-mouth disease in infants and occasionally severe neurological symptoms. Here we report that the product of L3HYPDH , a newly identified ISG, inhibits the replication of EV71. This anti-EV71 activity was mapped to the C-terminal 60 amino acids region as well as the N-terminal region spanning from amino acid position 61 to 120 of L3HYPDH protein. L3HYPDH was shown to interfere with EV71 propagation at the RNA replication and protein translation levels. Specifically, L3HYPDH impairs translation mediated by the EV71 international ribosome entry site (IRES) but not by the HCV IRES, and this activity is conferred by the C-terminal region of L3HYPDH. Thus, L3HYPDH has antiviral activity against EV71, suggesting a potential mechanism for broad-spectrum antiviral effects of IFN.
