GS5 and LH86 cells have been described earlier (32, 33) . Huh-7 and 293FT cells were maintained in DMEM supplemented with 10% FBS. We used the following antibodies: anti-CyPA (Biomol, Plymouth Meeting, PA, USA); anti-CyPB (AfEnity BioReagents, Rockford, IL, USA); anti-Ku80, anti-Flag and anti-actin (Sigma-Aldrich, St Louis, MO, USA); anti-IFN stimulate gene (ISG)15 (Rockland Immunochemicals, Gilbertsville, PA, USA); anti-NS5A (Virogen, Watertown, MA, USA) and anti-NS3 (in-house). GSB1 and H801 cells have been described earlier (34) . Poly I : C was purchased from Sigma-Aldrich, and synthetic hairpin RNA was purchased from Integrated DNA Technologies (Coralville, IA, USA). Synthetic siRNA was purchased from Ambion (Austin, TX, USA).