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

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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1511-1519
Number of pages9
JournalInternational Journal of Oncology
Volume39
Issue number6
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Adeno-associated virus
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Mouse model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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