Hepadnaviral infection augments hepatocyte cytotoxicity mediated by both CD95 ligand and perforin pathways

Liver International : Official Journal of the International Association for the Study of the Liver
Clifford S GuyTomasz I Michalak

Abstract

Recently, we documented that hepatocytes can eliminate contacted cells via the CD95 ligand (CD95L)-CD95 pathway and that they are also equipped in perforin and granzyme B and can eradicate other cells via the granule exocytosis mechanism. The aim of this study was to assess whether hepadnaviral infection modifies hepatocyte-mediated cell killing. Primary hepatocytes from woodchucks with progressing or resolved hepadnaviral hepatitis and hepatocyte lines transfected with woodchuck hepatitis virus (WHV) genes were examined for cytotoxic effector activity against cell targets susceptible to CD95L and/or perforin-dependent killing. Hepatocytes from healthy animals served as controls. Actively progressing and resolved hepadnaviral hepatitis is associated with a significantly greater capacity of hepatocytes to kill contacted cells. Both hepatocyte CD95L- and perforin-dependent cytotoxicity were augmented. Hepatocytes transfected with WHV X gene, but not those with complete WHV genome or virus envelope or core gene, transcribed significantly more CD95L and perforin and killed cell targets more efficiently. Exposure to interferon-gamma profoundly enhanced hepatocyte cell killing. Hepatocyte cytotoxic potential is significantly augmente...Continue Reading

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Citations

Jun 10, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Clifford S GuyTomasz I Michalak
Nov 20, 2013·Journal of Medical Virology·Masyelly D RojasSiham Salmen

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