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 Leung, M. Eric Gershwin, Mi Hua Tao

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)1511-1519
Number of pages9
JournalInternational Journal of Oncology
Volume39
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Dependovirus
Hepatitis B
Hepatitis B virus
Hepatocellular Carcinoma
Genes
Trans-Splicing
Liver Circulation
Virus Receptors
Liver
Chronic Hepatitis B
Virus Diseases
Virion
Hepatocytes
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery. / Huang, Ya Hui; Fang, Cheng Chieh; Tsuneyama, Koichi; Chou, Ho Yuan; Pan, Wen Yu; Shih, Yao Ming; Wu, Ping Yi; Chen, Yin; Leung, Patrick S; Gershwin, M. Eric; Tao, Mi Hua.

In: International Journal of Oncology, Vol. 39, No. 6, 12.2011, p. 1511-1519.

Research output: Contribution to journalArticle

Huang, Ya Hui ; Fang, Cheng Chieh ; Tsuneyama, Koichi ; Chou, Ho Yuan ; Pan, Wen Yu ; Shih, Yao Ming ; Wu, Ping Yi ; Chen, Yin ; Leung, Patrick S ; Gershwin, M. Eric ; Tao, Mi Hua. / A murine model of hepatitis B-associated hepatocellular carcinoma generated by adeno-associated virus-mediated gene delivery. In: International Journal of Oncology. 2011 ; Vol. 39, No. 6. pp. 1511-1519.
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