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hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs

  • Authors:
    • Ming Zhou
    • Bo Qin
    • Xue‑Song Deng
    • Xiao‑Li Zeng
    • Ying Lu
    • Zi‑Gang Huang
    • Chun‑Chen Wu
    • Li‑Sha Mou
  • View Affiliations / Copyright

    Affiliations: Shenzhen Xenotransplantation Research and Development Center, Institute of Translational Medicine, Health Science Center, Shenzhen University School of Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China, Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China, Department of Hepatobiliary Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China, Department of Internal Medicine, The Second People's Hospital of Futian District, Shenzhen, Guangdong 518049, P.R. China, Liver‑Biotechnology (Shenzhen) Co., Ltd., Shenzhen, Guangdong 518110, P.R. China, Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3820-3828
    |
    Published online on: August 29, 2019
       https://doi.org/10.3892/mmr.2019.10628
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Abstract

Primary human hepatocytes (PHHs) are the ‘gold standard’ for investigating hepatitis B virus (HBV) infection and antiviral drugs. However, poor availability, variation between batches and ethical issues regarding PHHs limit their applications. The discovery of human sodium taurocholate co‑transporting polypeptide (hNTCP) as a functional HBV receptor has enabled the development of a surrogate model to supplement the use of PHHs. In the present study, the evolutionary distance of seven species was assessed based on single‑copy homologous genes. Based on the evolutionary distance and availability, PHHs and primary rabbit hepatocytes (PRHs) were isolated and infected with hNTCP‑recombinant lentivirus, and susceptibility to HBV infection in the two cell types was tested and compared. In addition, HBV infection efficiency of hNTCP‑expressing PPHs with pooled HBV‑positive serum and purified particles was determined. The potential use of HBV‑infected hNTCP‑expressing PPHs for drug screening was assessed. The results demonstrated that pigs and rabbits are closer to humans in the divergence tree compared with mice and rats, indicating that pigs and rabbits were more likely to facilitate the HBV post‑entry lifecycle. Following hNTCP complementation and HBV infection, PPHs and Huh7D human hepatocellular carcinoma cells, but not PRHs, exhibited increased hepatitis B surface antigen and hepatitis B e‑antigen secretion, covalently closed circular DNA formation and infectious particle secretion. hNTCP‑expressing PPHs were susceptible to infection with HBV particles purified from pooled HBV‑positive sera, but were poisoned by raw HBV‑positive sera. The use of HBV‑infected hNTCP‑expressing PPHs for viral entry inhibitor screening was revealed to be applicable and reproducible. In conclusion, hNTCP‑expressing PPHs may be valuable tool for investigating HBV infection and antiviral drugs.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou M, Qin B, Deng XS, Zeng XL, Lu Y, Huang ZG, Wu CC and Mou LS: hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs. Mol Med Rep 20: 3820-3828, 2019.
APA
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z. ... Mou, L. (2019). hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs. Molecular Medicine Reports, 20, 3820-3828. https://doi.org/10.3892/mmr.2019.10628
MLA
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z., Wu, C., Mou, L."hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs". Molecular Medicine Reports 20.4 (2019): 3820-3828.
Chicago
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z., Wu, C., Mou, L."hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs". Molecular Medicine Reports 20, no. 4 (2019): 3820-3828. https://doi.org/10.3892/mmr.2019.10628
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou M, Qin B, Deng XS, Zeng XL, Lu Y, Huang ZG, Wu CC and Mou LS: hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs. Mol Med Rep 20: 3820-3828, 2019.
APA
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z. ... Mou, L. (2019). hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs. Molecular Medicine Reports, 20, 3820-3828. https://doi.org/10.3892/mmr.2019.10628
MLA
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z., Wu, C., Mou, L."hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs". Molecular Medicine Reports 20.4 (2019): 3820-3828.
Chicago
Zhou, M., Qin, B., Deng, X., Zeng, X., Lu, Y., Huang, Z., Wu, C., Mou, L."hNTCP‑expressing primary pig hepatocytes are a valuable tool for investigating hepatitis B virus infection and antiviral drugs". Molecular Medicine Reports 20, no. 4 (2019): 3820-3828. https://doi.org/10.3892/mmr.2019.10628
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