Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 1

► HCV core protein inhibits IRF-3 dimerization/phosphorylation, and IFN-β induction. ► The N-terminal region of the core protein inhibits the IFN signaling cascades. ► The N-terminal region, basic amino acid region 1 interferes with IRF-3 activation. ► DDX3 may be the core protein target for inhibiting IRF-3 activation. ► Rescue of the IRF-3 pathway impairment may be effective against HCV infection.