MxA inhibits hepatitis B virus replication by interaction with hepatitis B core antigen

Authors

  • Ning Li,

    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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    • These authors contributed equally to this work.

  • Lei Zhang,

    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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    • These authors contributed equally to this work.

  • Liangwei Chen,

    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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  • Wenfeng Feng,

    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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  • Yinfeng Xu,

    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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  • Feng Chen,

    1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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  • Xiaohong Liu,

    1. State Key Laboratory for Rice Biology, Biotechnology Institute, Zhejiang University, Hangzhou, Zhejiang, China
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  • Zhi Chen,

    1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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  • Wei Liu

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
    • Zhejiang University School of Medicine, Building B, Room 720, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058===

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    • fax: (86)-571-88208357


  • Potential conflict of interest: Nothing to report.

Abstract

Human 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. We investigated the molecular mechanism for the anti-HBV activity of MxA. Our results demonstrated that in HepG2.2.15 cells, MxA GTPase independently suppressed the production of hepatitis B surface antigen 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. 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 that may interfere with core particle formation. (HEPATOLOGY 2012;56:803–811)

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