(a) The innate immune induction pathway through RLR activation. HCV 5^'ppp RNA with poly-U/UC motif is shown as the RIG-I ligand RNA; 5^'ppp dsRNA is depicted beneath MDA5 and could serve as either RIG-I or MDA5 ligand RNA. The site of NS3/4A targeting of IPS-1 within the RLR pathway during HCV infection is indicated by the arrow, and the resulting signaling blockade is indicated by the broken line. (b) The RLR family members. CARD, helicase, and C-terminal domains, including the repressor domain (RD), are indicated. Numbers refer to amino acid (aa) length.