The ZBP-1 K43A mutant, but not the ZBP-1 K17A mutant, rescues ZBP-1 function in ZBP-1 knockout cells.A and B, ZBP1+/+ and ZBP1−/− THP-1 macrophages were transfected with siRNA-control (si-ctrl) or siRNA-TRIM34 and indicated plasmids for 24 h. Then, cells were infected with IAV (MOI = 1) for 24 h or left uninfected. IL-1β, IL-18, IL-6, and TNF-α protein levels in cell culture supernatants were determined by ELISA. C and D, experiments were performed as described in (A) and (B), except that the cells were transfected with vector control or Flag-TRIM34. E, experiments were performed as described in (A) and (C), except that cell death was quantified by LDH release. All experiments were repeated at least three times. Bar graphs present means ± SD, n = 3 (∗∗p < 0.01; n.s., not significant). IAV, influenza A virus; TRIM, tripartite motif; ZBP1, Z-DNA-binding protein 1.