title: Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein.
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.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine (BCM-385), One Baylor Plaza, Houston, TX 77030-3411, USA.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Keasler
authors.forename: Herve
authors.initials: H
authors.lastname: Lerat
authors.forename: Charles R
authors.initials: CR
authors.lastname: Madden
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McGarvey
authors.forename: Essam M A
authors.initials: EM
authors.lastname: Mohammed
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Hadsell
authors.forename: Shala J
authors.initials: SJ
authors.lastname: Grona
authors.forename: F Blaine
authors.initials: FB
authors.lastname: Hollinger
authors.forename: Betty L
authors.initials: BL
authors.lastname: Slagle
mesh_terms: D000818:Animals; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein