IFIT1 restricts viral infection posttranscriptionally by blocking the translation of viral mRNA (17, 27); therefore, we predicted that IFN-α–pretreated A549-ISG15−/− cells would remain susceptible to infection but that high levels of IFIT1 would mean these cells would not be permissive to PIV5 infection. Here, ISG15 is linked to viral infectious disease.