The influence of hepatitis C virus (HCV) protein(s) on cellular differentiation remains to be clarified. Using murine normal liver epithelial cells, we investigated whether HCV core protein affects differentiation into hepatocytes. Mock and HCV core-expressing cells were stimulated with oncostatin M (OSM) and dexamethasone, and the degree of differentiation was evaluated by measuring the expression of albumin and tyrosine aminotransferase (TAT). Lower amounts after stimulation were found in HCV core-expressing cells than in mock cells. Phosphorylation of the signal transducer and activator transcription factor 3 (STAT3) was prevented by the HCV core under OSM stimulation. Reporter gene assay revealed that the HCV core/Janus kinase (JAK) interaction directly suppressed the OSM-dependent JAK-STAT signal transduction. Furthermore, expression of OSM receptor P (OSMRP) after stimulation was prevented by the HCV core. In conclusion, the HCV core may suppress differentiation into hepatocytes via inhibition of the JAK-STAT pathway and OSMRO expression. (c) 2006 Elsevier Inc. All rights reserved.