Barriers to hepatitis C virus infection in mice

Hepatitis C virus (HCV) is unable to infect mice, a fact that has severely limited their use as small-animal models for HCV pathogenesis and as tools for HCV vaccine development. HCV is blocked at various stages of its life cycle in mouse cells, due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Molecular mechanisms for several such blocks have been characterized. The stepwise understanding of these limitations in mice will enable the development of an immunocompetent mouse that can fully support HCV infection and exhibit disease similar to that of infected humans. •In many countries, new hepatitis-C virus (HCV) infections outpace the number of patients cured with direct-acting antivirals.•A small-animal model for HCV would significantly accelerate vaccine development.•HCV’s exquisitely narrow host remains incompletely understood.•Incompatibilities between host and viral factors restrict HCV’s host tropism.•Innate immune responses restrict HCV infection in mice.