CD81 and hepatocellular carcinoma: Notably, we have previously shown that IFN-mediated activation of the innate cellular interferon response inhibits HCV RNA replication and subsequent production of de novo HCV virions ([45] and data not shown), thus the reduced steady-state HCVcc infection levels observed in Hep3B and HepG2-CD81 cells and the decline of HCV infection observed in PLC cells, despite these cells exhibiting comparable infection initiation permissiveness, may be at least in part a consequence of HCV-induced innate immune signaling in these hepatoma cell lines.