Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain

Authors

  • Bo Gao,

    1. Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, People's Republic of China
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    • These authors contributed equally to this work.

  • Zhijian Duan,

    1. Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, People's Republic of China
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    • These authors contributed equally to this work.

  • Wei Xu,

    1. Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, People's Republic of China
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  • Sidong Xiong

    Corresponding author
    1. Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, People's Republic of China
    2. Immunology Division, E-Institutes of Shanghai Universities, Shanghai, People's Republic of China
    • Institute for Immunobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China
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    • fax: (86)21-54237749


  • Potential conflict of interest: Nothing to report.

Abstract

Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. Conclusion: These findings suggest that TRIM22, which exhibits anti-HBV activity by acting as a transcriptional suppressor, may play an important role in the clearance of HBV. (HEPATOLOGY 2009.)

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