MxA Inhibits Hepatitis B Virus Replication By Interaction With Hepatitis B Core Antigen

Chronic hepatitis B virus (HBV) infection is a major risk factor for cirrhosis and hepatocellular carcinoma (HCC). In our country, more than50%of HCCs originate from the evolution of hepatitis B virus-related chronic hepatitis. Human myxovirus resistance protein A (MxA), an interferon-inducible cytoplasmic dynamin-like GTPase, possesses antiviral activity against multiple RNA viruses. Recently, MxA has also been demonstrated to have activity against the hepatitis B virus (HBV), a well-known DNA virus responsible for acute and chronic liver disease in humans. Here, we investigated the molecular mechanism for the anti-HBV activity of MxA. Our results demonstrated that in HepG2.2.15cells, MxA GTPase-independently suppressed the production of hepatitis B surface antigen (HBsAg) and HBV DNA without changing the level of hepatitis B core antigen (HBcAg) and the distribution of HBV mRNA. MxA significantly reduced the level of the encapsidated pregenomic RNA (pgRNA). Through its central interactive domain, MxA interacted with HBcAg causing accumulation of the proteins in perinuclear compartments. MxA-HBcAg interaction significantly affected the dynamics of HBcAg by immobilizing HBcAg in the perinuclear structures. Conclusion:MxA displays antiviral activity against HBV involving a mechanism of MxA-HBcAg interaction which may interfere with core particle formation. The findings provide a theoretical basis for the design of small molecules against HBV...