2004 Fiscal Year Final Research Report Summary
Preventive measure of the development of hepatocellular carcinoma by hepatitis C virus infection
| Project/Area Number |
12212001
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
SHIMOTOHNO Kunitada Institute for Vnus Research, Kyoto University, Professor, ウイルス研究所, 教授 (10000259)
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| Project Period (FY) |
2000 – 2004
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| Keywords | hepatitis C virus / apoptosis / genome / cyclophilin / TLR3 / innate immunity / replicon / nuclear receptor hormone |
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| Research Abstract |
Hepatitis C virus (HCV) is a causative agent for the development of chronic hepatitis. HCV infection is also shown to be an important agent for the development of hepatocellular carcinoma, but the precise mechanism for the development of these diseases remains to be elucidated. Current researches suggest the significant roles of HCV proteins on the disease progression. Thus, I have conducted experiments to analyze the roles of HCV protein on regulation of cell proliferation and disclosed the following evidence ; (1) HCV core protein has potential, to enhance NF-kB signaling, (2) HCV core protein enhances RARa dependent transcription by way of sequestration of transcriptional suppressor protein Sp110b, (3) HCV NS5A protein has function to regulate PKR by the interaction with PKR through the almost two-thirds of NS5A protein. For the preventive measure of HCV infection as well as for eradication of HCV from infected individuals, analysis of HCV genome replication in HCV genome self-replicating cells was conducted. And the following new finding was made by the analysis ; (1) replication of HCV genome seems to be conducted in a complex protected by ER derived membrane, which mainly localizes on ER, (2) replication of the HCV genome is strictly regulated by innate immunity signaling, in particular, those activated by TLR3, (3) HCV genome replication is positively regulated by cyclophilin B. Some of these information may be applicable for the development of a new agent with anti-HCV function.
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Research Products
(12 results)
