ISG15 and infection: In a control experiment, we found that some viral proteins, which did not interact with ISG15, UBE1L, and Herc5 in co-IP assays, could be ISGylated in co-transfection/ISGylation assays (S6 Fig), supporting the concept that viral proteins may be broadly ISGylated during infection due to IFN-upregulated expression of Herc5 (E3) in polyribosomes [41].