HCV-core protein accelerates recovery from the insensitivity of liver cells to Fas-mediated apoptosis induced by an injection of anti-Fas antibody inmice

Background/Aims: Hepatitis C virus (HCV) is a major etiologic agent of chro nic hepatitis, cirrhosis, and hepatocellular carcinoma. The aim of this stu dy 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 Pr-core mice. Results: HCV-core protein was detectable in livers from lines 5 (C5) and 8 (C8) of Pr-core transgenic mice. Since chronic hepatitis and cirrhosis prec ede hepatocellular carcinoma in patients with HCV infection, we tried to ex amine the effect of repetitive injection of a small dose of anti-Pas antibo dy in the transgenic mice. Surprisingly, an initial injection of anti-Fas a ntibody induced resistance of liver cells to the second injection of anti-P as antibody in both Pr-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 hepat ectomy. However, the sensitivity was restored in the Pr-core mice within 12 weeks after the injection. Conclusion: HCV-core protein in liver cells may affect persistence of Pas-m ediated liver cell injury.