To determine whether the TRIM56 E3 ligase enzymatic activity is required to induce IFNβ mRNA expression upon HSV-1ΔICP34.5 infection, we generated the enzymatically dead mutant (Mut) of TRIM56 by replacing the cysteine 21 and 24 residues with serines and complemented TRIM56−/− BMDMs with lentivirus-derived TRIM56WT or TRIM56 Mut (Supplementary Fig. 8b, Fig. 6e). Here, TRIM56 is linked to infection.