Jason Whitmire, PhD, Associate Professor in the Department of Genetics and Stanley Lemon, MD, Professor in the Department of Medicine, were senior authors on a paper titled “MAVS-dependent host species range and pathogenicity of human hepatitis A virus” published in the journal Science.
The paper, published in the 15 SEP 2016 issue of Science, described a murine model of hepatitis A virus (HAV) infection that mimics type A hepatitis in humans. The study demonstrated that the capacity of HAV to evade mitochondrial antiviral signaling (MAVS)-mediated type I interferon responses defined the host species range. HAV infection has long been thought to only occur in primates but interrupting the intrinsic viral response signaling pathways in mice allowed the virus to jump species, a key step in viral emergence. HAV-induced liver injury in the mouse model was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic inflammation resulting from MAVS and IRF3/7 signaling. This unexpected finding provides evidence for a link between innate immune responses to viral infection and acute liver injury. The team plans to define the interplay between innate and adaptive immune responses in this mouse model to better understand how HAV infection can be controlled.