RNA virus infection affects the location and possibly the function of microsomal epoxide hydrolase

Abstract

We have reported that the autoantibody to microsomal epoxide hydrolase (mEH) is induced during the course of hepatitis C and hepatitis A virus infection (J. Autoimmunity 28:7, 2007). The appearance of mEH in sera during the incubation period and the virus specificity of the antibody response suggested that mEH is somehow affected by virus replication rather than by hepatocyte damage. In this study, we have elucidated the effects of RNA virus replication on the location and biochemical function of mEH in cell lines.Human hepatocyte cell lines were infected with various RNA viruses or DNA viruses. They were also treated with poly (I:C) by adding to the medium or transfection. The mEH expression was analyzed by radioimmunoassay, immunofluorescence test, and western blotting. Metabolic activation of a carcinogen by these cells was evaluated by DMBA‐mediated cytotoxicity assay.mEH was found to appear on the cell surface after infection with RNA virus but not with DNA viruses whereas the whole amount of mEH did not change significantly. Such changes could also be induced by poly (I:C) treatment The cells which displayed surface expression of mEH exhibited more than ten‐times higher sensitivity to DMBA‐mediated cytotoxicity.These results suggest that RNA virus infection disrupts the distribution of mEH in the cells and affect the metabolic activation of polycyclic aromatic hydrocarbon carcinogens.