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

• Autores: Asuka Hirai Yuki, Lucinda Hensley, Olga González López
• Localización: Science, ISSN 0036-8075, Vol. 353, Nº 6307, 2016, págs. 1542-1545
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.