Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx

Frontiers in Immunology
Guangyun TanGenhong Cheng

Abstract

Hepatitis B virus (HBV) remains a major cause of hepatic disease that threatens human health worldwide. Type I IFN (IFN-I) therapy is an important therapeutic option for HBV patients. The antiviral effect of IFN is mainly mediated via upregulation of the expressions of the downstream IFN-stimulated genes. However, the mechanisms by which IFN induces ISG production and inhibits HBV replication are yet to be clarified. TRIM14 was recently reported as a key molecule in the IFN-signaling pathway that regulates IFN production in response to viral infection. In this study, we sought to understand the mechanisms by which IFN restricts HBV replication. We confirmed that TRIM14 is an ISG in the hepatic cells, and that the pattern-recognition receptor ligands polyI:C and polydAdT induce TRIM14 dependent on IFN-I production. In addition, IFN-I-activated STAT1 (but not STAT3) directly bound to the TRIM14 promoter and mediated the induction of TRIM14. Interestingly, TRIM14 played an important role in IFN-I-mediated inhibition of HBV, and the TRIM14 SPRY domain interacted with the C-terminal of HBx, which might block the role of HBx in facilitating HBV replication by inhibiting the formation of the Smc-HBx-DDB1 complex. Thus, our study clear...Continue Reading

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Citations

Mar 8, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongxiao SongZhengkun Tu
Jun 1, 2019·FEBS Open Bio·Jingang CuiWentao Qiao
Oct 30, 2019·The Journal of General Virology·Adam Hage, Ricardo Rajsbaum
May 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caitlyn T HoffpauirRobert O Watson
Nov 5, 2019·Frontiers in Microbiology·Fengchao XuGuangyun Tan
Apr 14, 2021·Cellular & Molecular Immunology·Hongxiao SongGuangyun Tan
Apr 4, 2021·European Journal of Immunology·Mengmeng GuoHaizhen Zhu
Sep 15, 2021·Journal of Cellular Biochemistry·Ankur R DubeyAmit Mishra

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Methods Mentioned

BETA
PCR
transfection
protein assay
ELISA
gene knockout
Assay
Immunoprecipitation
ChIP-PCR
ChIP
immunoprecipitation assay

Clinical Trials Mentioned

NCT01671787

Software Mentioned

TRANSFAC
[UNK] XRS + Molecular Imager
JASPAR

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