[Report] MAVS-dependent host species range and pathogenicity of human hepatitis A virus

Thursday, September 29, 2016 - 14:38 in Health & Medicine

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. Authors: Asuka Hirai-Yuki, Lucinda Hensley, David R. McGivern, Olga González-López, Anshuman Das, Hui Feng, Lu Sun, Justin E. Wilson, Fengyu Hu, Zongdi Feng, William Lovell, Ichiro Misumi, Jenny P.-Y. Ting, Stephanie Montgomery,...

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