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Hepatitis B virus X protein and its host partners

Cellular & Molecular Immunology volume 18, pages 1345–1346 (2021)Cite this article

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Hepatitis B virus (HBV) is a widespread human pathogen, especially in China, and is known to cause liver inflammation, cirrhosis, and hepatocellular carcinoma. A total of ten different genotypes of HBV (A–J) have been reported worldwide. HBV has partially double-stranded DNA, and the 3.2-kb viral genome is located in the nucleus of infected hepatocytes. All of the viral RNAs are transcribed from the covalently closed circular DNA (cccDNA), which acts as the transcription template. The seven main proteins of HBV include Core, pre-Core, Small S, Middle S, Large S, Polymerase, and the critical HBV-encoded regulatory protein hepatitis B virus X protein (HBx). HBx is a 154-amino acid (aa) protein that facilitates the efficient replication of HBV by stimulating HBV gene expression from the cccDNA template. However, the mechanism by which HBx interacts with host proteins and facilitates HBV replication is not precisely known.1,2

In our study, sought to identify several host factors, which are interferon-stimulated genes (ISGs) that regulate HBV replication and infection by targeting HBx.3,4,5 Using a bimolecular fluorescence complementation assay, we screened a group of ISGs that interacted with the HBx protein to inhibit HBV replication and found that CBFβ was the top-ranking ISG protein. CBFβ is a small molecule found to facilitate HIV replication by increasing the steady-state level of the viral infectivity factor protein.6 In our further study to clarify the mechanism involved in CBFβ induction by IFN, we found that CBFβ could not be upregulated by type I IFN in HepG2 cells. However, it has been previously reported that type III IFN production is induced after HBV infection;7 thus, we speculated that type III interferons might induce CBFβ. As we expected, CBFβ induction was confirmed in both the qPCR and immunoblot analyses, and we thus focused our research on the IFN-III-CBFβ-HBx-HBV axis.

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Acknowledgements

This work was supported by the National Natural Science Foundation, China (Grant Nos. 81901592 to H.S., 81801563 to Q.X., and 81801565 to F.X.), and the 68th batch of first-class funding from China Postdoctoral Science Foundation (Grant No. 2020M680044 to G.T.).

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  1. Department of Immunology, Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, Jilin, China

    Hongxiao Song, Fengchao Xu & Guangyun Tan

  2. Department of Nephrology, the First Hospital of Jilin University, Changchun, Jilin, China

    Qingfei Xiao

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  1. Hongxiao Song
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Correspondence to Guangyun Tan.

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Song, H., Xu, F., Xiao, Q. et al. Hepatitis B virus X protein and its host partners. Cell Mol Immunol 18, 1345–1346 (2021). https://doi.org/10.1038/s41423-021-00674-z

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