ウイルス感染における細胞内二本鎖RNA認識受容体の機能解析

2010 年度 研究成果報告書

• 研究領域: 感染現象のマトリックス
• 研究課題/領域番号: 18073010
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 京都大学 (2008-2010); 大阪大学 (2006-2007)
• 研究代表者: 藤田 尚志 京都大学, ウイルス研究所, 教授 (10156870)
• 研究期間 (年度): 2006 – 2010
• キーワード: ウイルス / 自然免疫 / インターフェロン / 遺伝子改変マウス / ヘリカーゼ

研究概要

細胞内二本鎖RNA認識受容体である(RIG-I-Like receptors, RLRと総称される)の機能を分子から個体のレベルで解析を行ない、RLRの認識するウイルス、それらに由来するRNAの構造、受容体の構造を明らかにした。またシグナル伝達の分子機構の解明を行なった。これらの成果はウイルス感染症の診断、治療への基礎を築くものである。

研究成果

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• [雑誌論文] Virus-Infection or 5'ppp-RNA Activates Antiviral Signal through Redistribution of IPS-1 Mediated by MFN1. (2010)
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• [雑誌論文] 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication (2010)
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  • 雑誌名: Virology Journal. 7 ページ: 102
• [雑誌論文] LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. (2010)
  • 著者名/発表者名: Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O.
  • 雑誌名: Proc Natl Acad Sci USA. 107 ページ: 1512-1517
• [雑誌論文] RIG-I activation inhibits ebolavirus replication. (2009)
  • 著者名/発表者名: Spiropoulou CF, Ranjan P, Pearce MB, Sealy TK, AlbarinoCG, Gangappa S, Fujita T, Rollin PE, Nichol ST, Ksiazek TG, Sambhara S.
  • 雑誌名: Virology. 392 ページ: 11-15
• [雑誌論文] RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. (2009)
  • 著者名/発表者名: Sato S., Hoshino K., Satoh T., Fujita T., Kawakami Y., Fujita T., Kuwana M.
  • 雑誌名: Arthritis & Rheumatism. 60 ページ: 2193-2200
• [雑誌論文] Solution Structures of MDA5 and LGP2 C-terminal Domains: Identification of the RNA Recognition Loop in RIG-I Like Receptors. (2009)
  • 著者名/発表者名: Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
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• [雑誌論文] Identification of loss of function mutations in human genes encoding RIG-I and mda5:Implications for resistance to type I diabetes. (2009)
  • 著者名/発表者名: Shigemoto T., Kageyama M., Hirai R., Zheng J-P., Yoneyama M., Fujita T.
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• [雑誌論文] Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. (2008)
  • 著者名/発表者名: Kato H., Takeuchi O., Mikamo-Satoh E., Hirai R., Kawai T,.Matsushita K., Hiiragi A., Dermody TS., Fujita T., Akira S.
  • 雑誌名: J Exp Med. 7 ページ: 1523-1527
• [雑誌論文] Non-self RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2008)
  • 著者名/発表者名: Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr.M., Inagaki F., Fujita T.
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• [雑誌論文] The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. (2008)
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  • 雑誌名: Molecular Cell. 29 ページ: 169-179
• [雑誌論文] Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. (2007)
  • 著者名/発表者名: Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.
  • 雑誌名: Proc Natl Acad Sci USA. 104 ページ: 7500-7505
• [雑誌論文] Katn of Intracytoplasmic Pathogen Sensor, RIG-I. (2007)
  • 著者名/発表者名: Guo Z., Chen L.M., Zeng H., Gomez J.A., Plowden J., Fujita T., Katz J.A., Plowden J., Fujita T.
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• [雑誌論文] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism. (2007)
  • 著者名/発表者名: Onoguchi K., Yoneyama M., Takemura A., Akira S., Taniguchi T., Namiki H., Fujita T.
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• [雑誌論文] Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. (2007)
  • 著者名/発表者名: Saito T., Hirai R., Loo Yueh-Ming., D Owen., C L.Johnson., S C.Shinha., Akira S., Fujita T., Gale Jr., M.
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• [雑誌論文] Differential role of MDA5 and RIG-I in the recognition of RNA viruses. (2006)
  • 著者名/発表者名: Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., Matsui K., Uematsu S., Jung A., Kawai T., Ishii K.J., Yamaguchi O., Otsu K., Tsujimura T., Koh C-S., Reis e Sousa C., Matsuura Y., Fujita T., Akira S.
  • 雑誌名: Nature 441 ページ: 101-105
• [学会発表] Virus-infection or 5´ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1. (2010)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Cytokines 2010:Cancer in Infectious Diseases, Autoimmune Disorders and Cancer.
  • 発表場所: Chicago, USA
  • 年月日: 20101003-20101007
• [学会発表] Regulation of the innate antiviral response by local condensation of IPS-1 mediated by mitochondrial dynamism. (2010)
  • 著者名/発表者名: Fujita T.
  • 学会等名: 50th ICAAC.
  • 発表場所: Boston, USA
  • 年月日: 20100912-20100915
• [学会発表] Regulation of the innate antiviral response by local condensation of IPS-1 mediated by mitochondrial dynamism. (2010)
  • 著者名/発表者名: Fujita T.
  • 学会等名: 14th International Congress of Immunology.
  • 発表場所: Kobe, Japan
  • 年月日: 20100822-20100827
• [学会発表] Recognition of viral nucleic acids by RLRs in antiviral innate immunity. (2010)
  • 著者名/発表者名: Fujita T.
  • 学会等名: 3rd International Workshop on Cell Communication in Health and Disease.
  • 発表場所: Vienna, Austria
  • 年月日: 20100217-20100218
• [学会発表] Mechanism of RNA recognition by the RIG-I-like receptors and activation of antiviral program: 2^nd International Centre for Genetic Engineering and Biotechnology Workshop on Human RNA viruses. (2010)
  • 著者名/発表者名: Fujita T.
  • 発表場所: New Dehli, India
  • 年月日: 20100210-20100212
• [学会発表] Activation of an antiviral program through the cytoplasmic Recognition of non-self RNA patterns by RLR. (2009)
  • 著者名/発表者名: Takashi Fujita
  • 発表場所: Tri-Society Annual Conference, Lisbon Portugal
  • 年月日: 2009-10-19
• [学会発表] Sensing Viral Replication by RIG-I-Like Receptors and Antiviral Innate Immunity. (2009)
  • 著者名/発表者名: Takashi Fujita
  • 学会等名: 109^th General Meeting of American Society for Microbiology
  • 発表場所: Philadelphia, USA
  • 年月日: 2009-05-19
• [学会発表] Solution Structures of MDA5 and LGP2 C-Terminal Domains: Identification of the RNA Recognition Loop in RIG-I Like Receptors. (2009)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Keystone Symposia, Pattern Recognition Molecules and Immune Sensors of Pathogens.
  • 発表場所: Banff, Canada
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• [学会発表] Mechanism of Foreign RNA Recognition in the Cytoplasm. (2008)
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  • 学会等名: 7^th Joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research.
  • 発表場所: Montreal Quebec, Canada
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• [学会発表] Non-self RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. (2008)
  • 著者名/発表者名: Fujita T.
  • 学会等名: 1^st International Centre for Genetic Engineering and Biotechnology Workshop on Human RNA viruses.
  • 発表場所: Trieste, Italy
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• [学会発表] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. (2008)
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  • 学会等名: XIV.International Congress of Virology
  • 発表場所: Istanbul, Turkey
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• [学会発表] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. (2008)
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• [学会発表] Regulation of interferon gene expression and virus infection of the liver. (2008)
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  • 発表場所: Moody Gardens Resort, Galveston, Texas
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• [学会発表] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2007)
  • 著者名/発表者名: Fujita T.
  • 学会等名: ISICR 2007
  • 発表場所: Oxford, UK
  • 年月日: 20070916-20070919
• [学会発表] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2007)
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  • 学会等名: 3rd Annual Meeting of the Oligonucleotide Therapeutic Society
  • 発表場所: Langenbeck-Virchow Auditorium, Berlin, Germany
  • 年月日: 2007-10-05
• [学会発表] RIG-I family helicases: Cytoplasmic sensor for non-self RNA.Viral Immunology Symposium (2007)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Johns Hopkins Bloomberg School of Public Health, Baltimore
  • 発表場所: MD USA
  • 年月日: 2007-07-23
• [学会発表] Sensing viruses and antiviral response. (2007)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Gordon Research Conferences: Viruses and Cells
  • 発表場所: Tilton School, Tilton NH USA
  • 年月日: 2007-06-05
• [学会発表] Triggering Antiviral responses and Cell Regulation by the Cytoplasmic RNA Helicase RIG-I. (2007)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Keystone Symposia: Intracellular and Intercellular Signaling in Dendritic Cell Function
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  • 年月日: 2007-02-26
• [学会発表] Signal Transduction by Cytoplasmic Virus Receptors. (2007)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Keystone Symposia: Jaks, Stats and Immunity
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• [学会発表] Triggering Antiviral Responses and host regulation by the Cytoplasmic RNA Helicase RIG-I. (2006)
  • 著者名/発表者名: Fujita T.
  • 学会等名: Cytokines 2006
  • 発表場所: Vienna, Austria
  • 年月日: 2006-08-28
• [図書] Chapter 2 Type I interferon production by viruses, in Viruses and Interferon: Current Research, Ed. (2010)
  • 著者名/発表者名: Kazuhide Onoguchi, Kiyohiro Takahasi, Mitsutoshi Yoneyama, Takashi Fujita
  • 出版者: Karen Mossman, Caister Academic Press
• [備考] ホームページ等
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/bunshiiden/index.html