To avoid mistakenly identifying ubiquitin or NEDD8 sites as ISG15 sites (due to possible indirect effects of Isg15 deletion or USP18C61A/C61A mutation), we assessed whether ubiquitin and NEDD8 levels appear to vary using SDS-PAGE prior to or following infection (Supplementary Fig. 1a, b). Here, NEDD8 is linked to infection.