Development of preventive measures of liver failures caused by HCV infection by clarification of the mechanisms of liver diseases

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Hepatitis C virus is a major causative agent for development of various liver failures including chronic hepatitis and hepatocellular carcinoma. One of the major problem of the developing such liver failures by HCV is persistent nature of HCV infection. In fact, those of individuals who became free from HCV infection by interferon treatment were cured from HCV associated liver failures thereafter. Thus, the development of efficient anti-HCV agents is one goal to prevent HCV related liver diseases. In addition, clarification of the mechanism of the development of liver failures contributes to establish preventive measures for onset of HCV-related diseases. Aims in this work are, therefore, firstly, to understand detail mechanisms of HCV proliferation to obtain insights of the knowledge to develop anti-HCV agents and, secondary, to reveal the mechanisms of the development of liver failure which contributes to develop measures to prevent exacerbation of liver diseases. In this work, I discovered following evidences; (1) Cyclosporin A inhibited HCV genome replication efficiently through impairing the function of cyclophilins, (2) a new ubiquitin E3 ligase which regulats interferon signaling was discovered, (3) HCV infection dys-regulated lipid metabolism as well as lipid transfer mechanism. And this dys-regulation is important for efficient replication of HCV. (4) Dys-regulation of lipid metabolisms and lipoprotein transfer mechanism may contribute to exacerbate of liver failure and, therefore, regulation of lipid metabolism will be therapeutics for not only prevent liver diseases but also prevent HCV proliferation.