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SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions

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Abstract

Chronic hepatitis B virus (HBV) infection remains a significant public health concern worldwide. Several metabolic processes regulate HBV DNA replication, including autophagy and lipid metabolism. In this study, we clarified the effect of lipids on HBV replication and elucidated possible mechanisms. We discovered that lipid metabolic gene expression levels were negatively correlated with the HBV DNA in plasma. Our data showed that fatty acid stimulation significantly reduced HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) levels in HepG2.2.15 cells, which are human hepatoma cell cultures transfected with HBV DNA. The Stearoyl coenzyme A desaturase 1 (SCD1)-autophagy pathway has also been implicated in inhibiting HBV replication by fatty acids stimulation. SCD1 knockdown deregulates the inhibitory effect of fatty acids on HBV by enhancing autophagy. When 3 methyladenine (3MA) was added, the inhibitory effects of specific autophagy inhibitors eliminated the positive effects of SCD1 knockdown on HBV replication. Our results indicate that SCD1 participates in the regulation of inhibition of HBV replication by fatty acids stimulation through regulating autophagy.

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Data availability

The datasets generated during and analyzed during the current study are available in the jianguoyun repository, https://www.jianguoyun.com/p/Dd_-95gQioqdCxjVwewEIAA

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Acknowledgements

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Funding

This present work was funded by the Bethune Charitable Foundation (Grant No. B19036GN).

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Author notes

  1. Xuan Du and Xiaoyi Shi have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China

    Xuan Du, Mei Han & Chunmeng Jiang

  2. Graduate School of Dalian Medical University, Dalian, 116000, China

    Xiaoyi Shi & Chuang Wang

  3. Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, China

    Xiaoyun Gao

  4. Department of Biobank, The Affiliated Sixth People’s Hospital of Dalian Medical University, Dalian, 116000, China

    Chunwen Pu

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Contributions

CJ and CP: designed the project. XD: carried out the bioinformatics analysis. XS: conducted the experiments. XD and XS: wrote this article together. MH and XG: participated in the data analysis. CW: collected the clinical data. All authors participated in revising and discussing the content of this article and approved the submitted version.

Corresponding authors

Correspondence to Chunmeng Jiang or Chunwen Pu.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

The clinical data analysis of this study was approved by the Ethics Committee of the Second Affiliated Hospital of Dalian Medical University. The data of bioinformatics analyzed in this study were from public databases. All methods in this study were performed in accordance with the relevant guidelines and regulations.

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Du, X., Shi, X., Han, M. et al. SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions. Virus Genes 59, 801–816 (2023). https://doi.org/10.1007/s11262-023-02028-5

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