A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery

  • Authors:
    • Ya-Hui Huang
    • Cheng-Chieh Fang
    • Koichi Tsuneyama
    • Ho-Yuan Chou
    • Wen-Yu Pan
    • Yao-Ming Shih
    • Ping-Yi Wu
    • Yin Chen
    • Patrick S.C. Leung
    • M. Eric Gershwin
    • Mi-Hua Tao
  • View Affiliations

  • Published online on: July 28, 2011     https://doi.org/10.3892/ijo.2011.1145
  • Pages: 1511-1519
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Abstract

A relevant animal model is critical for investigating the pathogenic mechanisms underlying hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Mice are not naturally infected by HBV, presumably due to the lack of HBV receptors on mouse hepatocytes. To bypass this entry step of HBV infection, we report generation of a novel HBV model in immunocompetent mice by hepatic delivery of the HBV genome using trans-splicing adeno-associated viral vectors (AAV/HBV). We confirmed production of HBV virions and proteins in the liver and circulation in all AAV/HBV-transduced mice in all four immunocompetent mouse strains tested. These mice produced antigen and antibody profiles similar to that observed in chronic HBV patients. Importantly, 12-16 months later, all 12 AAV/HBV-transduced mice developed macroscopically visible liver-tumor nodules. Ten of the twelve tumors were characterized with typical HCC features. This AAV/HBV-transduced murine HCC model provides a useful instrument for studying the pathogenesis of HBV-associated HCC and the development of HCC therapeutic interventions.

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December 2011
Volume 39 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Huang, Y., Fang, C., Tsuneyama, K., Chou, H., Pan, W., Shih, Y. ... Tao, M. (2011). A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery. International Journal of Oncology, 39, 1511-1519. https://doi.org/10.3892/ijo.2011.1145
MLA
Huang, Y., Fang, C., Tsuneyama, K., Chou, H., Pan, W., Shih, Y., Wu, P., Chen, Y., Leung, P. S., Gershwin, M. E., Tao, M."A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery". International Journal of Oncology 39.6 (2011): 1511-1519.
Chicago
Huang, Y., Fang, C., Tsuneyama, K., Chou, H., Pan, W., Shih, Y., Wu, P., Chen, Y., Leung, P. S., Gershwin, M. E., Tao, M."A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery". International Journal of Oncology 39, no. 6 (2011): 1511-1519. https://doi.org/10.3892/ijo.2011.1145