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Aborted infection of human sodium taurocholate cotransporting polypeptide (hNTCP) expressing woodchuck hepatocytes with hepatitis B virus (HBV)

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Abstract

Due to the limited host range of HBV, research progress has been hindered by the absence of a suitable animal model. The natural history of woodchuck hepatitis virus (WHV) infection in woodchuck closely mirrors that of HBV infection in human, making this species a promising candidate for establishing both in vivo and in vitro HBV infection models. Therefore, this animal may be a valuable species to evaluate HBV vaccines and anti-HBV drugs. A significant milestone in HBV and hepatitis D virus (HDV) infection is the discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the functional receptor. In an effort to enhance susceptibility to HBV infection, we introduced hNTCP into the woodchuck hepatocytes by multiple approaches including transduction of vLentivirus-hNTCP in woodchuck hepatocytes, transfection of p-lentivirus-hNTCP-eGFP plasmids into these cells, as well as transduction of vAdenovirus-hNTCP-eGFP. Encouragingly, our findings demonstrated the successful introduction of hNTCP into woodchuck hepatocytes. However, it was observed that these hNTCP-expressing hepatocytes were only susceptible to HDV infection but not HBV. This suggests the presence of additional crucial factors mediating early-stage HBV infection that are subject to stringent species-specific restrictions.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the Prof. Bruno Stieger who gave us the hNTCP antibody.

Funding

This work was supported by the National Natural Science Foundation of China (81860113) and Shenzhen Science and Technology Program Project (JCYJ20190812172005670).

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Authors and Affiliations

  1. Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Lu Yang, Di Zhou & Jingjiao Song

  2. Department of Infectious Disease, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

    Jun Wu & Dongliang Yang

  3. Institute of Virology, Technische Universität München, Munich, Germany

    Kächele Martin, Ulrike Protzer & Michael Roggendorf

  4. Institute of Virology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany

    Mengji Lu

  5. Department of Infectious Diseases, Shenzhen Luohu People’s Hospital, The Third Affiliated Hospital, Shenzhen University, Shenzhen, People’s Republic of China

    Mingfa Chen

Authors
  1. Lu Yang
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  2. Di Zhou
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  3. Kächele Martin
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  4. Jun Wu
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  10. Jingjiao Song
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Contributions

JS designed the experiments, performed the experiments, MC and LY analyzed the data, DZ and JW did the statistical analysis. DZ, LY and JS carried out experiments. JS and LY wrote the paper. ML, DY, UP and R.M. conceived the experiments and revised the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jingjiao Song.

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The authors declare no conflict of interest.

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Yang, L., Zhou, D., Martin, K. et al. Aborted infection of human sodium taurocholate cotransporting polypeptide (hNTCP) expressing woodchuck hepatocytes with hepatitis B virus (HBV). Virus Genes 59, 823–830 (2023). https://doi.org/10.1007/s11262-023-02031-w

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  • DOI: https://doi.org/10.1007/s11262-023-02031-w

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