We demonstrated that combining a deleted thymidine kinase gene with truncations in immunomodulatory proteins C6 (interacts with NAP1, TANK, and SINTBAD [39]), N2 (blocks nuclear translocation of P-IRF3 [40]), or C10 (prevents dsDNA recognition by DNA-PK [41]) did not translate into IRF3 phosphorylation after cell infection; these three deletions needed to be combined in one virus (named WR/TK-/3Δ) in order detect IRF3 activation and subsequent type I interferon expression. This evidence concerns the gene TBKBP1 and infection.