In vivo studies of immune responses to infection with hepatitis C virus (HCV) have been hampered by the lack of suitable small animal models. In Science, Billerbeck et al. characterize immune responses in mice to an HCV-related hepacivirus originally found in street rats. Wild-type mice develop acute liver infection that can be cleared within several weeks, whereas immunocompromised mice establish chronic viral infection. Interferon and CD4+ T cell help are necessary for viral clearance, as mice transiently depleted of CD4+ cells develop chronic infection despite the generation of effector CD8+ T cells. Whereas clearance of acute infection is accompanied by substantial liver damage, chronic infection elicits mild liver inflammation and more intrahepatic regulatory T cells and exhausted CD8+ T cells. Use of this mouse model should enhance efforts to develop effective therapies and vaccines directed against HCV.

Science 357, 204–208 (2017)