Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein

Virology. 2006 Apr 10;347(2):466-75. doi: 10.1016/j.virol.2005.11.050. Epub 2006 Jan 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / genetics
  • Hepatitis C / pathology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology*
  • Liver / virology
  • Mice
  • Mice, Transgenic
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins


  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein