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

• DOI: 10.1126/science.aaf8325
• Publication Date: 2016-09-16T04:13:41Z
• 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; John Cullen; Jason K. Whitmire; Stanley M. Lemon
• Keywords: IRF3; Pathogenesis; Liver disease

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