HEPATITIS-C VIRUS CORE AND E2 PROTEIN EXPRESSION IN TRANSGENIC MICE

Transgenic mice have been produced that express the hepatitis C virus (HCV) core protein in the liver under the transcriptional control of t he mouse major urinary protein promoter. These animals express the ful l length core protein in cytoplasm of their hepatocytes at levels comp arable to those detected in naturally infected patients, without histo logical or biochemical evidence of Liver disease or hepatocellular car cinoma. This contrasts with recent reports that HCV core protein can t ransform NIH 3T3 cells and cooperates with H-ras to transform primary rat fibroblasts in vitro. Coexpression of HCV core protein in double t ransgenic mice that replicate the hepatitis B virus (HBV) does not inh ibit hepatocellular HBV gene expression or replication, contrary to re ports that it inhibits HBV replication in HuH-7 cells after transient transfection in vitro. We have also produced transgenic mice in which a C-terminally truncated (aa384-715) glycosylated HCV E2 protein is ex pressed in the liver under the transcriptional control of the mouse al bumin promoter. Despite the high level expression of HCV E2 protein, n o evidence of Liver disease was detected in these animals. These resul ts suggest that the HCV core and E2 proteins are not cytopathic for th e hepatocyte in vivo and they represent an initial step in the develop ment of a small animal model of HCV immunopathology.