DEVELOPMENT OF HEPATITIS THERAPY AND VACCINE USING HEPATITIS C VIRUS TRANSGENIC MICE

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Hepatitis C virus(HCV), a major causative agent of non-A, non-B chronic hepatitis, is also suggested to be associated with extrahepatic manifestations such as mixed cryoglobulinemia and glomerulonephritis. Two independent lines of transgenic mice carrying the HCV envelope genes have been previously shown to express the HCV envelope proteins in organs including the liver and salivary glands, which results in no pathological changes in the liver. Further analysis of these animals has now revealed that they develop an exocrinopathy involving the salivary and lachrymal glands. This pathology resembles Sjogren's syndrome, which is also suggested to have a possible association with chronic hepatitis C.These observations suggest that HCV may be involved in the pathogenesis of sialadenitis in humans, and this transgenic mouse system would be a good animal model for the study of HCV infection.HCV has been known to finally leads to the development of hepatocellular carcinoma (HCC). However, the mechanism of hepatocarcinogenesis in chronic HCV infection is still unclear. The ability of the core protein of HCV to modulate intracellular signaling pathways has been suggested as being involved in the pathogenesis of HCC.Here we describe the development of HCC in HCV core gene transgenic mice which develop hepatic steatosis early in life as a histological feature characteristic of chronic hepatitis C.The feature in the development of HCC in these mice closely resembled the histopathological characteristics previously observed in the early stage of HCC in patients with chronic hepatitis C.These results indicate that the HCV core protein has a major role in the development of HCC and that HCV itself is directly involved in hepatocarcinogenesis.