(A) HEK293 cells were transfected with MDA5 and PACT expression plasmids for 48 h. Total lysate was subjected to pull-down with poly(I:C)- or polyC-conjugated agarose beads. Bound fraction and input were analyzed by Western blotting. (B) A poly(I:C) pull-down experiment was carried out with endogenous MDA5 and PACT. HEK293 cells were mock treated or treated with rIFN-β (1000 U/ml) for 24 h before harvest. (C and D) HEK293 cells were transfected with MDA5 and PACT expression plasmids, alone or in combination, for 30 h before poly(I:C) stimulation (1 μg/ml). Coimmunoprecipitation was carried out with anti-V5 (C) or anti-FLAG (D) Ab. (E) HEK293 cells carrying a stably expressed IFN-β–luc were transfected with expression plasmids for MDA5 and either PACT-WT or its dsRNA-binding defective mutant (PACT-M1, PACT-M2, or PACT-DM) for 24 h, followed by poly(I:C) induction (1 μg/ml) for 6 h. Protein expression was validated by Western blotting (inset). *p < 0.01 versus PACT-WT, Student t test.