| 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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| Co-Investigator(Kenkyū-buntansha) |
小池 和彦 東京大学, 医学研究科, 助教授 (80240703)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥70,200,000 (Direct Cost: ¥70,200,000)
Fiscal Year 2004: ¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2003: ¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2001: ¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2000: ¥18,000,000 (Direct Cost: ¥18,000,000)
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| Keywords | hepatitis C virus / apoptosis / genome / cyclophilin / TLR3 / innate immunity / replicon / nuclear receptor hormone / ウイルスポリメラーゼ / HCVゲノムレプリコン複製 / インターフェロン / ゲノム / 複製 / サイクロスポリン / 肝がん / 細胞増殖 / PKR / リン酸化 / NS5A / トランスジェニックマウス / 脂肪代謝 / コアタンパク質 / NF-kB / 小胞体膜 |
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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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