Type I-IFN plays a critical role in the innate immune response as the first line of defense against enterovirus infection and regulates many immune responsive genes, including IFN-β, IFI-27, ISG15, and OAS-1 (Schoggins et al., 2011; Wu and Chen, 2014; Roers et al., 2016). This evidence concerns the gene ISG15 and enterovirus infectious disease.