Deficiencies in type I IFN signaling, either via Ifnar1-deficiency or deficiency of Irf3, Irf5, and Irf7 such that little IFN is produced, have been key to modeling ZIKV infection in mice and recapitulating aspects of human disease, supporting a critical role for type I IFN in controlling ZIKV infection [179,180,181]. This evidence concerns the gene IRF3 and Zika virus infectious disease.