title: HCV-core protein accelerates recovery from the insensitivity of liver cells to Fas-mediated apoptosis induced by an injection of anti-Fas antibody in mice.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) is a major etiologic agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The aim of this study was to elucidate pathological effects of HCV-core protein on liver cells.
  
  
  METHODS
  We have generated transgenic mice carrying HCV-core cDNA (Px-core) and pathologically examined livers of Px-core mice.
  
  
  RESULTS
  HCV-core protein was detectable in livers from lines 5 (C5) and 8 (C8) of Px-core transgenic mice. Since chronic hepatitis and cirrhosis precede hepatocellular carcinoma in patients with HCV infection, we tried to examine the effect of repetitive injection of a small dose of anti-Fas antibody in the transgenic mice. Surprisingly, an initial injection of anti-Fas antibody induced resistance of liver cells to the second injection of anti-Fas antibody in both Px-core and littermate control mice. The insensitivity of liver cells induced in the control mice continued for more than 24 weeks after the first injection but was broken within 1 week after partial hepatectomy. However, the sensitivity was restored in the Px-core mice within 12 weeks after the injection.
  
  
  CONCLUSIONS
  HCV-core protein in liver cells may affect persistence of Fas-mediated liver cell injury.
authors.affiliation: Department of Developmental Genetics, Chiba University Graduate School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Honda
authors.forename: M
authors.initials: M
authors.lastname: Hatano
authors.forename: M
authors.initials: M
authors.lastname: Kohara
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Hartatik
authors.forename: T
authors.initials: T
authors.lastname: Moriyama
authors.forename: M
authors.initials: M
authors.lastname: Imawari
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
authors.forename: K
authors.initials: K
authors.lastname: Shimotohno
authors.forename: T
authors.initials: T
authors.lastname: Tokuhisa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004351:Drug Resistance; D015870:Gene Expression; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D013997:Time Factors; D014758:Viral Core Proteins / Q000235:genetics / Q000494:pharmacology*; D019014:fas Receptor / Q000276:immunology* / Q000502:physiology*
chemical_list: D000906:Antibodies; D014758:Viral Core Proteins; D019014:fas Receptor; C069130:nucleocapsid protein, Hepatitis C virus