In an attempt to establish a model for hepatitis C virus (HCV) infection, we produced mice transgenic for the HCV envelope genes, E1 and E2, under the control of a regulatory element from hepatitis B virus. F-generation mice from the established founders demonstrated expression of both E1 and E2 proteins as glycosylated forms in their organs including the liver. Immunostaining revealed the localization of envelope proteins principally in the cytoplasm of hepatocytes around the hepatic central veins. Furthermore, E1 and E2 proteins were shown by immunoprecipitation to be associated with each other in the mouse liver. There was no evidence of tissue pathology in the mouse liver up to 16 months of age, suggesting that E1 and E2 proteins may not have direct pathogenic effects. Our results demonstrate the first successful expression of HCV gene products in the mouse liver and the association of expressed HCV envelope proteins. This transgenic mouse would be a good model to study the virus-cell interactions of HCV such as intracellular transport and assembly of envelope proteins. Also it may be a good model system to determine the role of these proteins in the pathogenesis of hepatitis or extra-hepatic manifestations in HCV infection by the introduction of cytotoxic T lymphocytes specific for the envelope proteins.


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