Function of cytoplasmic double-stranded RNA sensor in viral infection

2010 Fiscal Year Final Research Report

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073010
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2008-2010); Osaka University (2006-2007)
• Principal Investigator: FUJITA Takashi Kyoto University, ウイルス研究所, 教授 (10156870)
• Project Period (FY): 2006 – 2010
• Keywords: 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

Research Abstract

We analyzed the function of RIG-I-Like receptor (collectively termed as RLR). RLR functions as cytoplasmic receptors for RNA derived from viral replication. Our results elucidate virus specificity of each RLR, the RNA structures recognized by RLR and molecular mechanism of viral RNA recognition. These result will be critical bases for developing diagnosis and treatment of viral infections.

Research Products

• [Journal Article] Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. (2010)
  • Author(s): Slater L, Bartlett NW, Haas JJ, Zhu J, Message SD, Walton RP, Sykes A, Dahdaleh S, Clarke DL, Belvisi MG, Kon OM, Fujita T, Jeffery PK, Johnston SL, Edwards MR.
  • Journal Title: PLoS Pathog. 6(11) Pages: e1001178
• [Journal Article] Virus-Infection or 5'ppp-RNA Activates Antiviral Signal through Redistribution of IPS-1 Mediated by MFN1. (2010)
  • Author(s): Onoguchi K, Onomoto K, Takamatsu S, Jogi M, Takemura A, Morimoto S, Julkunen I, Namiki H, Yoneyama M, Fujita T.
  • Journal Title: PLoS Pathog. 6(7) Pages: e1001012
• [Journal Article] 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication (2010)
  • Author(s): Ranjan P, Jayashankar L, Deyde V, Zeng H, Davis WG, Pearce MB, Bowzard JB, Hoelscher MA, Jeisy-Scott V, Wiens ME, Gangappa S, Gubareva L, Garcia-Sastre A, Katz JM, Tumpey TM, Fujita T, Sambhara S.
  • Journal Title: Virology Journal. 7 Pages: 102
• [Journal Article] LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. (2010)
  • Author(s): Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O.
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 1512-1517
• [Journal Article] RIG-I activation inhibits ebolavirus replication. (2009)
  • Author(s): Spiropoulou CF, Ranjan P, Pearce MB, Sealy TK, AlbarinoCG, Gangappa S, Fujita T, Rollin PE, Nichol ST, Ksiazek TG, Sambhara S.
  • Journal Title: Virology. 392 Pages: 11-15
• [Journal Article] 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)
  • Author(s): Sato S., Hoshino K., Satoh T., Fujita T., Kawakami Y., Fujita T., Kuwana M.
  • Journal Title: Arthritis & Rheumatism. 60 Pages: 2193-2200
• [Journal Article] Solution Structures of MDA5 and LGP2 C-terminal Domains: Identification of the RNA Recognition Loop in RIG-I Like Receptors. (2009)
  • Author(s): Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
  • Journal Title: J.Biol.Chem 284 Pages: 17465-17474
• [Journal Article] Identification of loss of function mutations in human genes encoding RIG-I and mda5:Implications for resistance to type I diabetes. (2009)
  • Author(s): Shigemoto T., Kageyama M., Hirai R., Zheng J-P., Yoneyama M., Fujita T.
  • Journal Title: J.Biol.Chem[Epub ahead of print]
• [Journal Article] Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. (2008)
  • Author(s): Kato H., Takeuchi O., Mikamo-Satoh E., Hirai R., Kawai T,.Matsushita K., Hiiragi A., Dermody TS., Fujita T., Akira S.
  • Journal Title: J Exp Med. 7 Pages: 1523-1527
• [Journal Article] Non-self RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2008)
  • Author(s): Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr.M., Inagaki F., Fujita T.
  • Journal Title: Molecular Cell. 29 Pages: 428-440
• [Journal Article] The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. (2008)
  • Author(s): Cui S., Eisenacher K., Kirchhofer A., Brzozka K., Lammens A., Lammens K., Fujita T., Conzelmann K-K., Krug A., Hopfner K-P.
  • Journal Title: Molecular Cell. 29 Pages: 169-179
• [Journal Article] Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. (2007)
  • Author(s): Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.
  • Journal Title: Proc Natl Acad Sci USA. 104 Pages: 7500-7505
• [Journal Article] Katn of Intracytoplasmic Pathogen Sensor, RIG-I. (2007)
  • Author(s): Guo Z., Chen L.M., Zeng H., Gomez J.A., Plowden J., Fujita T., Katz J.A., Plowden J., Fujita T.
  • Journal Title: Am J Respir Cell Mol Biol. 36 Pages: 263-269
• [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism. (2007)
  • Author(s): Onoguchi K., Yoneyama M., Takemura A., Akira S., Taniguchi T., Namiki H., Fujita T.
  • Journal Title: J.Biol.Chem 282 Pages: 7576-7581
• [Journal Article] Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. (2007)
  • Author(s): Saito T., Hirai R., Loo Yueh-Ming., D Owen., C L.Johnson., S C.Shinha., Akira S., Fujita T., Gale Jr., M.
  • Journal Title: Proc.Natl.Acad.Sci.USA 104 Pages: 582-587
• [Journal Article] Differential role of MDA5 and RIG-I in the recognition of RNA viruses. (2006)
  • Author(s): 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.
  • Journal Title: Nature 441 Pages: 101-105
• [Presentation] Virus-infection or 5´ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1. (2010)
  • Author(s): Fujita T.
  • Organizer: Cytokines 2010:Cancer in Infectious Diseases, Autoimmune Disorders and Cancer.
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101003-20101007
• [Presentation] Regulation of the innate antiviral response by local condensation of IPS-1 mediated by mitochondrial dynamism. (2010)
  • Author(s): Fujita T.
  • Organizer: 50th ICAAC.
  • Place of Presentation: Boston, USA
  • Year and Date: 20100912-20100915
• [Presentation] Regulation of the innate antiviral response by local condensation of IPS-1 mediated by mitochondrial dynamism. (2010)
  • Author(s): Fujita T.
  • Organizer: 14th International Congress of Immunology.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-20100827
• [Presentation] Recognition of viral nucleic acids by RLRs in antiviral innate immunity. (2010)
  • Author(s): Fujita T.
  • Organizer: 3rd International Workshop on Cell Communication in Health and Disease.
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20100217-20100218
• [Presentation] 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)
  • Author(s): Fujita T.
  • Place of Presentation: New Dehli, India
  • Year and Date: 20100210-20100212
• [Presentation] Activation of an antiviral program through the cytoplasmic Recognition of non-self RNA patterns by RLR. (2009)
  • Author(s): Takashi Fujita
  • Place of Presentation: Tri-Society Annual Conference, Lisbon Portugal
  • Year and Date: 2009-10-19
• [Presentation] Sensing Viral Replication by RIG-I-Like Receptors and Antiviral Innate Immunity. (2009)
  • Author(s): Takashi Fujita
  • Organizer: 109^th General Meeting of American Society for Microbiology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2009-05-19
• [Presentation] Solution Structures of MDA5 and LGP2 C-Terminal Domains: Identification of the RNA Recognition Loop in RIG-I Like Receptors. (2009)
  • Author(s): Fujita T.
  • Organizer: Keystone Symposia, Pattern Recognition Molecules and Immune Sensors of Pathogens.
  • Place of Presentation: Banff, Canada
  • Year and Date: 2009-04-01
• [Presentation] Mechanism of Foreign RNA Recognition in the Cytoplasm. (2008)
  • Author(s): Fujita T.
  • Organizer: 7^th Joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research.
  • Place of Presentation: Montreal Quebec, Canada
  • Year and Date: 20081012-20081016
• [Presentation] Non-self RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. (2008)
  • Author(s): Fujita T.
  • Organizer: 1^st International Centre for Genetic Engineering and Biotechnology Workshop on Human RNA viruses.
  • Place of Presentation: Trieste, Italy
  • Year and Date: 20080930-20081003
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. (2008)
  • Author(s): Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr.M., Inagaki F.and Fujita T.
  • Organizer: XIV.International Congress of Virology
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 20080810-20080815
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. (2008)
  • Author(s): Fujita T.
  • Organizer: Keystone Symposia, Innate Immunity: Signaling Mechanisms.
  • Place of Presentation: Keystone, Colorado
  • Year and Date: 20080224-20080229
• [Presentation] Regulation of interferon gene expression and virus infection of the liver. (2008)
  • Author(s): Fujita, T.
  • Organizer: Hepatic Inflammation and Immunity.
  • Place of Presentation: Moody Gardens Resort, Galveston, Texas
  • Year and Date: 20080125-20080127
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2007)
  • Author(s): Fujita T.
  • Organizer: ISICR 2007
  • Place of Presentation: Oxford, UK
  • Year and Date: 20070916-20070919
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2007)
  • Author(s): Fujita T.
  • Organizer: 3rd Annual Meeting of the Oligonucleotide Therapeutic Society
  • Place of Presentation: Langenbeck-Virchow Auditorium, Berlin, Germany
  • Year and Date: 2007-10-05
• [Presentation] RIG-I family helicases: Cytoplasmic sensor for non-self RNA.Viral Immunology Symposium (2007)
  • Author(s): Fujita T.
  • Organizer: Johns Hopkins Bloomberg School of Public Health, Baltimore
  • Place of Presentation: MD USA
  • Year and Date: 2007-07-23
• [Presentation] Sensing viruses and antiviral response. (2007)
  • Author(s): Fujita T.
  • Organizer: Gordon Research Conferences: Viruses and Cells
  • Place of Presentation: Tilton School, Tilton NH USA
  • Year and Date: 2007-06-05
• [Presentation] Triggering Antiviral responses and Cell Regulation by the Cytoplasmic RNA Helicase RIG-I. (2007)
  • Author(s): Fujita T.
  • Organizer: Keystone Symposia: Intracellular and Intercellular Signaling in Dendritic Cell Function
  • Place of Presentation: Keystone, CO USA
  • Year and Date: 2007-02-26
• [Presentation] Signal Transduction by Cytoplasmic Virus Receptors. (2007)
  • Author(s): Fujita T.
  • Organizer: Keystone Symposia: Jaks, Stats and Immunity
  • Place of Presentation: Steamboat Springs, CO USA
  • Year and Date: 2007-01-09
• [Presentation] Triggering Antiviral Responses and host regulation by the Cytoplasmic RNA Helicase RIG-I. (2006)
  • Author(s): Fujita T.
  • Organizer: Cytokines 2006
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2006-08-28
• [Book] Chapter 2 Type I interferon production by viruses, in Viruses and Interferon: Current Research, Ed. (2010)
  • Author(s): Kazuhide Onoguchi, Kiyohiro Takahasi, Mitsutoshi Yoneyama, Takashi Fujita
  • Publisher: Karen Mossman, Caister Academic Press
• [Remarks] ホームページ等
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/bunshiiden/index.html