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

Journal Article · Mon Apr 10 00:00:00 EDT 2006 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2005.1· OSTI ID:20779483

Keasler, Victor V ^[1]; Lerat, Herve ^[1]; Madden, Charles R ^[1]; Finegold, Milton J ^[2]; McGarvey, Michael J ^[3]; Mohammed, Essam M.A. ^[3]; Forbes, Stuart J ^[3]; Lemon, Stanley M ^[4]; Hadsell, Darryl L ^[5]; Grona, Shala J ^[1]; Hollinger, F Blaine ^[1]; Slagle, Betty L ^[1]

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1. Department of Molecular Virology and Microbiology, Baylor College of Medicine (BCM-385), One Baylor Plaza, Houston, TX 77030-3411 (United States)
2. Department of Pathology, Baylor College of Medicine, Houston, TX 77030-3411 (United States)
3. Division of Medicine, Imperial College London, London (United Kingdom)
4. Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1019 (United States)
5. Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-3411 (United States)

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.

• OSTI ID: 20779483
• Journal Information: Virology, Vol. 347, Issue 2; Other Information: DOI: 10.1016/j.virol.2005.11.050; PII: S0042-6822(05)00793-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
APOPTOSIS
DEATH
GENES
HEPATITIS
HEPATOMAS
LIVER
LIVER CELLS
PATHOGENESIS
PATHOLOGY
PROTEINS
TRANSGENIC MICE
VIRUSES