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Peptide YY inhibits transcription and replication of hepatitis B virus by suppressing promoter/enhancer activity

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Abstract

Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor.

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Data availability

The datasets supporting the conclusions of this article are available in the SRA (www.ncbi.nlm.nih.gov/sra) database.

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Funding

Sponsored by the Natural Science Foundation of Liaoning Province of China (2022-MS-409), Science and Technology Innovation Project of Shenyang (RC210215), Foundation of Liaoning Educational Committee (LJKQZ2021176) and the Innovation Fund of Shenyang medical college (Y20220508).

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Author notes

  1. Xiaolun Xu and Weiping Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathogen Biology, Shenyang Medical College, Shenyang, China

    Xiaolun Xu, Weiping Zhou, Jun Cao, Ye Sun, Biao Yang, Xueqian Li, Yanting Li, Chunmeng Zhang & Guangyan Liu

  2. Department of Physiology, Shenyang Medical College, Shenyang, China

    Xing Tian

  3. Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang, China

    Zhongjia Jiang

  4. Department of Immunology, Shenyang Medical College, Shenyang, China

    Xuanhe Fu

Authors
  1. Xiaolun Xu
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  2. Weiping Zhou
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  3. Xing Tian
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  4. Zhongjia Jiang
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  5. Xuanhe Fu
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  9. Xueqian Li
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  10. Yanting Li
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  11. Chunmeng Zhang
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  12. Guangyan Liu
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Contributions

XX, WZ, XL, CZ and YL: data acquisition. XX, WZ, XL, BY and YS: data analysis and interpretation. XX, XT, ZJ, XF, JC and GL: manuscript preparation. GL: study conception and design, study super vision. WZ, GL: funding acquisition. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Guangyan Liu.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the Ethics Committees of the First Hospital of China Medical University (No. AF-SOP-07-1.1-01).

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Edited by Juergen Richt.

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Xu, X., Zhou, W., Tian, X. et al. Peptide YY inhibits transcription and replication of hepatitis B virus by suppressing promoter/enhancer activity. Virus Genes 59, 678–687 (2023). https://doi.org/10.1007/s11262-023-02017-8

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  • DOI: https://doi.org/10.1007/s11262-023-02017-8

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