期刊
JOURNAL OF GENERAL VIROLOGY
卷 96, 期 -, 页码 614-625出版社
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.070680-0
关键词
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资金
- French Ministry for Higher Education and Research (Ministere de l'Enseignement Superieur et de la Recherche)
- Bill and Melinda Gates Foundation
- Fondation de la Recherche Medicale (FRM)
- Institut Nationale de la Sante et de la Recherche Medicale (Inserm)
- Association de la Recherche contre le Cancer (ARC) [5054]
- Association Nationale de Recherche sur le sida et les hepatites virales (ANRS) [06202]
Hepatitis B virus X protein (HBx) is involved in the development of hepatocellular carcinoma (HCC). The HBx sequence is a preferential site of integration into the human genome, leading to the formation of C-terminal-truncated HBx proteins (Ct-HBx). We previously reported that Ct-HBx proteins were able to potentiate cell transformation in vitro. Our present goal was to compare the ability of Ct-HBx and full-length HBx (FL-HBx) proteins to develop or enhance HCC in transgenic mice. In the absence of treatment, neither Ct-HBx- nor FL-HBx-transgenic mice developed HCC. In young mice treated with diethylnitrosamine (DEN) at 8 months of age, a significantly higher incidence and number of liver lesions were observed in Ct-HBx mice than in FL-HBx and control mice. The earlier development of tumours in Ct-HBx-transgenic mice was associated with increased liver inflammation. At 10 months, macroscopic and microscopic analyses showed that, statistically, FL-HBx mice developed more liver lesions with a larger surface area than control mice. Furthermore, during DEN-induced initiation of HCC, Ct-HBx- and FL-HBx-transgenic mice showed higher expression of IL-6, TNF-alpha and IL-1 beta transcripts, activation of STAT3, ERK and JNK proteins and an increase in cell apoptosis. In conclusion, in DEN-treated transgenic mice, the expression of Ct-HBx protein causes a more rapid onset of HCC than does FL-HBx protein. HBV genome integration leading to the expression of a truncated form of HBx protein may therefore facilitate HCC development in chronically infected patients.
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