title: Hepatitis C virus structural proteins induce liver cell injury in transgenic mice.
abstract: To develop an animal model of hepatitis C virus (HCV) infection, transgenic mice carrying part of the HCV cDNA (C980) encoding HCV-core and envelope proteins under control of the mouse class I major histocompatibility complex gene (H-2K) regulatory region were produced. HCV-C980 RNA and HCV-core protein were present in livers from line H36 as determined by RNase protection assay and immunostaining, respectively. More than 40 animals from line H36 were examined histologically. Most of these H36 mice after 10 months of age developed spontaneous focal infiltration of lymphocytes, hepatocyte necrosis, degeneration, and altered foci with mitotic hepatocytes. These pathological lesions were absent in livers from the age-matched control littermates. Liver cells from these H36 mice were sensitive to damage induced by intravenous administration of an anti-Fas antibody. It is suggested that HCV-C980 proteins by themselves may be one causative agent of liver cell injury in subjects with HCV infection.
authors.affiliation: Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: N
authors.initials: N
authors.lastname: Hirota
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Ikegaki
authors.forename: T
authors.initials: T
authors.lastname: Koizumi
authors.forename: M
authors.initials: M
authors.lastname: Hatano
authors.forename: M
authors.initials: M
authors.lastname: Kohara
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: Shimotohno
authors.forename: T
authors.initials: T
authors.lastname: Tokuhisa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics; D006526:Hepatitis C / Q000821:virology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000032:analysis; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D015678:Viral Structural Proteins / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D012367:RNA, Viral; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; D000509:alpha-Fetoproteins; D019014:fas Receptor