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.
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.
Honda
A
A
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Japan.
Hatano
M
M
Kohara
M
M
Arai
Y
Y
Hartatik
T
T
Moriyama
T
T
Imawari
M
M
Koike
K
K
Yokosuka
O
O
Shimotohno
K
K
Tokuhisa
T
T
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*
D000906:Antibodies; D014758:Viral Core Proteins; D019014:fas Receptor; C069130:nucleocapsid protein, Hepatitis C virus