Although the EV71 3C protein has been reported to down-regulate IFN-β transcription through interactions with host RIG-I protein or cleavage of the TRIF protein, an adaptor protein for TLR3 signaling [42], [45], we observed that MDA5, not RIG-I, was degraded in cells that had been infected with the MP4, the TW2231/98, and the BrCr strains of EV71, and that the MDA5 cleavage was dependent on the caspase activation upon EV71 infection, in a manner similar to that observed in poliovirus infection [40]. The gene discussed is IFIH1; the disease is poliovirus infection.