Recapitulation of the hepatitis C virus life-cycle in engineered murine cell lines

- HCV NS3/4A protease cleaves mouse MAVS and TRIF.
- Type I and III signaling interferes with HCV RNA replication.
- Infection of mouse cells expressing human HCV entry factors.
- Assembly and release of infectious particles in murine cells.
- Completion of the entire HCV life-cycle in mouse cells.

Hepatitis C virus (HCV) remains a major medical problem. In-depth study of HCV pathogenesis and immune responses is hampered by the lack of suitable small animal models. The narrow host range of HCV remains incompletely understood. We demonstrate that the entire HCV life-cycle can be recapitulated in mouse cells. We show that antiviral signaling interferes with HCV RNA replication in mouse cells. We were able to infect mouse cells expressing human CD81 and occludin (OCLN)-the minimal set of entry factor factors required for HCV uptake into mouse cells. Infected mouse cells sustain HCV RNA replication in the presence of miR122 and release infectious particles when mouse apoE is supplied. Our data demonstrate that the barriers of HCV interspecies transmission can be overcome by engineering a suitable cellular environment and provide a blue-print towards constructing a small animal model for HCV infection.