Chronic Hepatitis B virus infections affect about 350 million people worldwide and constitute a significant risk factor for fibrosis and hepatocellular carcinoma (HCC). HBV alters mitochondrial dynamics. HBV has been shown to induce autophagy of mitochondria (Mitophagy) as evidenced by Parkin translocation to mitochondria. We propose to investigate a possible link between mitochondrial dynamics induced by HBV and innate immunity. HBV cripples host innate immunity to maintain chronic persistent infection. Here, we propose to investigate the molecular mechanisms of HBV- induced suppression of innate immune signaling from mitochondrial platform. The key player in this process is a mitochondrial antiviral signaling protein (MAVS). There is sufficient supporting information, which shows that Parkin, an E3 ubiquitin ligase, interacts with MAVS on the mitochondria and that Parkin causes the ubiquitination of MAVS. These investigations will elucidate how MAVS is targeted by Parkin in a supracomplex and affects downstream antiviral signaling of interferon synthesis. These interactions and ubiquitinations eventually cripple innate immunity. These studies will provide unique insights into molecular mechanisms of HBV-induced mitochondrial dynamics and its effects on altering host innate immune response and open new avenues of investigations in the elucidation of innate immune pathways.
Chronic Hepatitis B virus infections affect about 350 million people worldwide and are a major risk factor for fibrosis and hepatocellular carcinoma (HCC). This proposal focuses on the role of HBV in altering the mitochondrial dynamics and its impact on host innate immunity leading to chronic liver injury associated with HBV infection.
| Kim, Seong-Jun; Ahn, Dae-Gyun; Syed, Gulam H et al. (2018) The essential role of mitochondrial dynamics in antiviral immunity. Mitochondrion 41:21-27 |
