A murine model of hepatitis A virus infection demonstrated that HAV evasion of MAVS-mediated type I interferon responses defines its host species range and links innate immunity to acute liver injury.
This murine model reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.
Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis viruses is poorly understood because of a lack of tractable small- animal models. We describe a murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. We demonstrate that the capacity of HAV to evade MAVS-mediated type I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation that unexpectedly resulted from MAVS and IRF3/7 signaling. This murine model thus reveals a previously undefined link between innate immune responses to virus infection and acute liver injury, providing a new paradigm for viral pathogenesis in the liver.
Hirai-Yuki et al. (Fri,) conducted a other in Hepatitis A virus infection. A murine model of hepatitis A virus infection demonstrated that HAV evasion of MAVS-mediated type I interferon responses defines its host species range and links innate immunity to acute liver injury.