Viral hepatitis is an important cause of global morbidity but no small animal models replicate human virus-induced liver disease. Hepatitis A (HAV), as with HBV and HCV, is restricted to humans and nonhuman primates as the virus encodes proteinases that degrade MAVS — a molecule involved in the induction of type I interferons that restrict HAV replication. However, because human MAVS sequences are not conserved in small mammals, Hirai-Yuki et al. hypothesized that the restricted host range of HAV stems from an inability to evade MAVS-mediated interferon responses. The researchers show that mice lacking interferon receptors were highly permissive to HAV infection, which accurately recapitulated the features of hepatitis A in humans. Thus, these data provide a tool for studying HAV infection that could be relevant to other hepatotropic viruses.