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United States Department of Agriculture

Agricultural Research Service

Title: Increased Liver Pathology in Hepatitis C Virus Transgenic Mice Expressing the Hepatitis B Virus X Protein

Authors
item Keasler, Victor - BAYLOR COLLEGE MED
item Lerat, Herve - BAYLOR COLLEGE MED
item Madden, Charles - BAYLOR COLLEGE MED
item Finegold, Milton - BAYLOR COLLEGE MED
item Mcgarvey, Michael - IMPERIAL COLL LONDON, UK
item Mohammed, Essam - IMPERIAL COLL LONDON, UK
item Forbes, Stuart - IMPERIAL COLL LONDON, UK
item Lemon, Stanley - UNIV TEXAS MEDICAL BRANCH
item Hadsell, Darryl - BAYLOR COLLEGE MED
item Grona, Shala - BAYLOR COLLEGE MED
item Hollinger, F - BAYLOR COLLEGE MED
item Slagle, Betty - BAYLOR COLLEGE MED

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 30, 2005
Publication Date: April 10, 2006
Citation: Keasler, V.V., Lerat, H., Madden, C.R., Finegold, M.J., McGarvey, M.J., Mohammed, E.M., Forbes, S.J., Lemon, S.M., Hadsell, D.L., Grona, S.J., Hollinger, F.B., Slagle, B.L. 2006. Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein. Virology. 346(2):466-475.

Interpretive Summary: Chronic hepatitis is a common and serious condition in the US. This condition frequently produces liver cancer and is often the result of interactions among different hepatitis virus strains. The goal of this study was to determine if specific hepatitis viral proteins interact to produce cancer at greater rates. For this study transgenic mice were produced to overexpress two specific hepatits viral proteins that are believed to be responsible for liver disease. When these two proteins were overexpressed in the liver they accelerated the rate of liver cancer. These studies may help researchers understand how viruses cause fatty livers and liver cancer.

Technical Abstract: Transgenic mice expressing the full-length HCV coding sequence were crossed with mice that express the HBV X gene-encoded regulatory protein HBx (ATX mice) to test the hypothesis that HBx expression accelerates HCV-induced liver pathogenesis. At 16 months (mo) of age, hepatocellular carcinoma was identified in 21% of HCV/ATX mice, but in none of the single transgenic animals. Analysis of 8-mo animals revealed that, relative to HCV/WT mice, HCV/ATX mice had more severe steatosis, greater liver-to-body weight ratios, and a significant increase in the percentage of hepatocytes staining for proliferating cell nuclear antigen. Furthermore, primary hepatocytes from HCV, ATX, and HCV/ATX transgenic mice were more resistant to fas-mediated apoptosis than hepatocytes from nontransgenic littermates. These results indicate that HBx expression contributes to increased liver pathogenesis in HCV transgenic mice by a mechanism that involves an imbalance in hepatocyte death and regeneration within the context of severe steatosis.

Last Modified: 10/1/2014
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