Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis B virus X protein transgenic mice

2006 ◽  
Vol 340 (3) ◽  
pp. 916-928 ◽  
Author(s):  
Bo-Kuan Wu ◽  
Chao-Chin Li ◽  
Huei-Jane Chen ◽  
Junn-Liang Chang ◽  
King-Song Jeng ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Regenerating Liver ◽  
X Protein ◽  
B Virus

Transgenic mice expressing hepatitis B virus X protein are more susceptible to carcinogen induced hepatocarcinogenesis

2004 ◽  
Vol 76 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Huanzhang Zhu ◽  
Yun Wang ◽  
Jianquan Chen ◽  
Guoxiang Cheng ◽  
Jinglun Xue
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
X Protein ◽  
B Virus

Diagnosis of biliary duct cysts in transgenic mice expressing the hepatitis B virus X-protein

2004 ◽  
Vol 40 (2) ◽  
pp. 356-357 ◽  
Author(s):  
Olaf Dirsch ◽  
Florian Rödicker ◽  
Christoph U Herborn ◽  
Gero Hilken ◽  
Brigitte M Pützer
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Biliary Duct ◽  
X Protein ◽  
B Virus

scholarly journals Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice

2000 ◽  
Vol 74 (11) ◽  
pp. 5266-5272 ◽  
Author(s):  
Charles R. Madden ◽  
Milton J. Finegold ◽  
Betty L. Slagle
Keyword(s):  
Dna Repair ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Spontaneous Mutations ◽  
Environmental Carcinogens ◽  
X Protein ◽  
B Virus ◽  
The Impact

ABSTRACT Chronic infection with hepatitis B virus (HBV) is one of the major etiological factors in the development of human hepatocellular carcinoma. Transgenic mice that express the HBV X protein (HBx) have previously been shown to be more sensitive to the effects of hepatocarcinogens, although the mechanism for this cofactor role remains unknown. The ability of HBx to inhibit DNA repair in transiently transfected cell lines suggests one possible pathway. In the present study, primary hepatocytes isolated from transgenic mice that possess the HBV X gene under the control of the human α-1-antitrypsin regulatory region (ATX mice) were found to be deficient in their ability to conduct unscheduled DNA synthesis in response to UV-induced DNA damage. In order to measure the impact of HBx expression on DNA repair in vivo, double-transgenic mice that express HBx and possess a bacteriophage lambda transgene were sacrificed at 30, 90, and 240 days of age. Mutation frequency was determined for high-molecular-weight liver DNA of ATX and control mice by functional analysis of the lambda transgene. Expression of HBx did not significantly increase the accumulation of spontaneous mutations. These results are consistent with previous studies of HBx transgenic mice in which no effect of HBx on liver histology was apparent. This new animal model provides a powerful system in which to investigate the in vivo cooperation between HBx expression and environmental carcinogens.

scholarly journals Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice

2002 ◽  
Vol 76 (5) ◽  
pp. 2579-2584 ◽  
Author(s):  
Zhenming Xu ◽  
T. S. Benedict Yen ◽  
Lanying Wu ◽  
Charles R. Madden ◽  
Wenjie Tan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
X Protein ◽  
Multifunctional Protein ◽  
Hbv Replication ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) X gene encodes a multifunctional protein that can regulate cellular signaling pathways, interact with cellular transcription factors, and induce hepatocellular oncogenesis. In spite of its diverse activities, the precise role of the X protein in the viral life cycle of HBV remains unclear. To investigate this question, we have produced transgenic mice that carry either the wild-type HBV genome or a mutated HBV genome incapable of expressing the 16.5-kDa X protein. Our results indicate that while the X protein is not absolutely essential for HBV replication or its maturation in transgenic mice, it can enhance viral replication, apparently by activating viral gene expression. These results demonstrate a transactivation role of the X protein in HBV replication in transgenic mice.

Hepatitis B virus X protein enhances the development of liver fibrosis and the expression of genes associated with epithelial-mesenchymal transitions and tumor progenitor cells

2019 ◽  
Vol 41 (3) ◽  
pp. 358-367 ◽  
Author(s):  
James Ahodantin ◽  
Bouchra Lekbaby ◽  
Myriam Bou Nader ◽  
Patrick Soussan ◽  
Dina Kremsdorf
Keyword(s):  
Hepatitis B Virus ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Epithelial Mesenchymal Transition ◽  
Biological Effects ◽  
Matrix Remodeling ◽  
X Protein ◽  
Mesenchymal Transition ◽  
B Virus

Abstract The hepatitis B virus X protein (HBx) has pleiotropic biological effects, which underlies its potential role in cell transformation. However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic for the full-length HBx (FL-HBx) were used. To create liver fibrosis, FL-HBx transgenic and control mice were chronically exposed to carbon tetrachloride (CCl4). Modulation of the expression of proteins involved in matrix remodeling, hepatic metabolism and epithelial-mesenchymal transition (EMT) were investigated. In transgenic mice, FL-HBx expression potentiates CCl4-induced liver fibrosis with increased expression of proteins involved in matrix remodeling (Collagen1a, α-Sma, PdgfR-β, MMP-13). In FL-HBx transgenic mice, an increase in EMT was observed with a higher transcription of two inflammatory cytokines (TNF-α and TGF-β) and a decrease of glutamine synthetase expression level. This was associated with a sustained cell cycle and hepatocyte polyploidy alteration consistent with p38 and ERK1/2 overactivation, increase of PLK1 transcription, accumulation of SQSTM1/p62 protein and increase expression of Beclin-1. This correlates with a higher expression of tumor progenitor cell markers (AFP, Ly6D and EpCam), indicating a higher risk of progression from fibrosis to hepatocellular carcinoma (HCC) in the presence of FL-HBx protein. In conclusion, our results show that FL-HBx protein enhances the development of liver fibrosis and contributes to the progression of liver disease from chronic hepatitis to HCC.

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