ISG15 and infection: Consistent with this result, immunoblotting assays showed that the N(K261R) mutant virus expressed higher levels of the viral spike (S) and N proteins than its parental virus in IFN-β-treated cells, although a comparable increase of ISG15 and ISGylated protein levels was found in IFN-β-treated Calu-3 cells after infection with the wild-type or the N(K261R) mutant (Figure 6C).