Molecular machinery for recognition of viral ribonucleoprotein complex (RNP) by host innate immune receptors

• Project/Area Number: 23390108
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Chiba University
• Principal Investigator: YONEYAMA Mitsutoshi 千葉大学, 真菌医学研究センター, 教授 (40260335)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: ウイルス / 自然免疫 / RNA

Outline of Final Research Achievements

In this research project, we tried to reveal how viral RNA sensors, RIG-I-like receptors (RLRs), recognize replication-competent viral ribonucleoprotein complexes (RNPs) that are formed in virus-infected cells. We established in vitro reconstitution assay system to detect activation of RIG-I-mediated signaling in response to substrate RNAs, such as 5’-triphosphate-containing synthetic RNAs. As a result of investigations using viral RNPs of influenza A virus (IAV) as substrates, we clearly observed activation of RIG-I-mediated signaling by IAV RNPs in vitro. These results could help us to understand how anti-viral innate immune responses are initiated in virus-infected cells.

Research Products

• [Journal Article] Antiviral innate immunity and stress granule responses. (2014)
  • Author(s): Onomoto K, Yoneyama M, Fung G, Kato H, Fujita T.
  • Journal Title: Trends Immunol. Volume: 35 Issue: 9 Pages: 420-428
  • DOI: 10.1016/j.it.2014.07.006
  • Peer Reviewed
• [Journal Article] A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection. (2014)
  • Author(s): Narita R, Takahasi K, Murakami E, Hirano E, Yamamoto SP, Yoneyama M, Kato H, Fujita T.
  • Journal Title: PLoS Pathog. Volume: 10 Issue: 10 Pages: 1-11
  • DOI: 10.1371/journal.ppat.1004417
  • Peer Reviewed / Open Access
• [Journal Article] DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation (2014)
  • Author(s): Yoo, J-S., Takahasi, K., Ng, CS., Ouda, R., Onomoto, K., Yoneyama, M., Lai, J-C., Lattmann, S., Nagamine, Y., Matsui, T., Iwabuchi, K., Kato, H. Fujita, T.
  • Journal Title: PLoS Pathog Volume: 10(3) Issue: 3 Pages: 1-18
  • DOI: 10.1371/journal.ppat.1004012
  • NAID: 120005466661
  • Peer Reviewed / Open Access
• [Journal Article] EMCV disrupts stress granules, the critical platform for triggering antiviral innate immune responses. (2013)
  • Author(s): Ng CS, Jogi M, Yoo JS, Onomoto K, Koike S, Iwasaki T, Yoneyama M, Kato H, Fujita T.
  • Journal Title: J. Virol. Volume: 87 Issue: 17 Pages: 9511-9522
  • DOI: 10.1128/jvi.03248-12
  • Peer Reviewed
• [Journal Article] Functional characterization of domains of IPS-1 using an inducible oligomerization system (2013)
  • Author(s): Takamatsu S,Onoguchi K, Onomoto K, Narita R, Takahasi K, Ishidate F, Fujiwara TK, Yoneyama M, Kato H, Fujita T
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1371/journal.pone.0053578
  • NAID: 120005241348
  • Peer Reviewed
• [Journal Article] Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type-I interferon-dependent innate immunity (2013)
  • Author(s): Nitta S, Sakamoto N, Nakagawa M, Kakinuma S, Mishima K, Kusano-kitazume A, Kiyohashi K, Murakawa M, Nishimura-Sakurai Y, Azuma S, Tasaka-Fujita M, asahina Y, Yoneyama M, Fujita T, Watanabe M
  • Journal Title: Hepatology Volume: 57 Issue: 1 Pages: 46-58
  • DOI: 10.1002/hep.26017
  • Peer Reviewed
• [Journal Article] Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity (2012)
  • Author(s): Onomoto K, Jogi M, Yoo J-S, Narita R, Morimoto S, Takemura A, Sambhara S, Kawaguchi A, Osari S, Nagata K, Matsumiya T, Namiki H, Yoneyama M, Fujita T
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: 1-15
  • DOI: 10.1371/journal.pone.0043031
  • Peer Reviewed
• [Journal Article] Foreign RNA induces the degradation of mitochondrial antiviral signaling protein (MAVS)the role of intracellular antiviral factors. (2012)
  • Author(s): Xing F, Matsumiya T, Onomoto K, Hayakari R, Imaizumi T, Yoshida H, Yoneyama M, Fijita T, Satoh K
  • Journal Title: PLoS One Volume: 7(9) Issue: 9 Pages: e45136-e45136
  • DOI: 10.1371/journal.pone.0045136
  • Peer Reviewed
• [Journal Article] Impairment of interferon regulatoroy factor-3 activation by hepatitis C virus core protein basic amino acid region 1. (2012)
  • Author(s): Inoue K, Tsukiyama-Kohara K, Matsuda C, Yoneyama M, Fujita T, Kuge S, Yoshida M, Kohara M
  • Journal Title: Bichem Biophys Res Commun Volume: 428 Issue: 4 Pages: 494-499
  • DOI: 10.1016/j.bbrc.2012.10.079
  • Peer Reviewed
• [Journal Article] Retinoic Acid-inducible Gene I-inducible miR-23b Inhibits Infections by Minor Group Rhinoviruses through Down-regulation of the Very Low Density Lipoprotein Receptor (2011)
  • Author(s): Ouda R, Onomoto K, Takahasi K, Edwards MR, Kato H, Yoneyama M, Fujita T
  • Journal Title: Journal of Biological Chemistry Volume: 286 Issue: 29 Pages: 26210-26219
  • DOI: 10.1074/jbc.m111.229856
  • Peer Reviewed
• [Journal Article] 55 amino acid linker between helicase and carboxyl terminal domains of RIG-I functions as a critical repression domain and determines inter-domain conformation (2011)
  • Author(s): Kageyama M, Takahasi K, Narita R, Hirai R, Yoneyama M, Kato H, Fujita T
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 415 Issue: 1 Pages: 75-81
  • DOI: 10.1016/j.bbrc.2011.10.015
  • Peer Reviewed
• [Presentation] Regulation of anti-viral innate responses by host RNA binding proteins. (2014)
  • Author(s): M. Yoneyama
  • Organizer: The International Symposium "Molecular basis of host cell competency in virus infection" 2014
  • Place of Presentation: Pacifico Yokohama（神奈川県・横浜市）
  • Year and Date: 2014-11-08 – 2014-11-09
  • Invited
• [Presentation] 宿主RNA結合タンパク質によるウイルス感染応答制御 (2014)
  • Author(s): 米山光俊
  • Organizer: 第79回日本インターフェロン・ サイトカイン学会学術集会
  • Place of Presentation: 北海道大学医学部学友会館フラテホール（北海道・札幌市）
  • Year and Date: 2014-06-19 – 2014-06-20
  • Invited
• [Presentation] 細胞内ウイルスRNAセンサーによる感染検知の分子機構 (2014)
  • Author(s): 米山光俊
  • Organizer: 第15回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 名古屋市立大学大学院薬学研究科・宮田専治記念ホール（愛知県・名古屋市）
  • Year and Date: 2014-05-23 – 2014-05-24
  • Invited
• [Presentation] ウイルス感染に応答した自然免疫誘導の分子機構 (2012)
  • Author(s): 米山光俊
  • Organizer: 第１回千葉大学感染症研究ネットワーク研究会
  • Place of Presentation: 千葉
  • Invited
• [Presentation] Stress granule-like aggregates play a critical role in anti-viral innate immunity. (2012)
  • Author(s): Yoneyama M
  • Organizer: The 11th Awaji international Forum on Infection and Immunity
  • Place of Presentation: Awaji, Japan
  • Invited
• [Presentation] 自然免疫センサーRLRによるウイルス由来非自己RNA検知の分子機構 (2012)
  • Author(s): 米山光俊
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Analysis of Intracellular Localization of Viral RNA Sensor, RLR (2012)
  • Author(s): Onomoto K, Fujita T, Yoneyama M
  • Organizer: The 22nd CDB Meeting “RNA Sciences in Cell
  • Place of Presentation: 神戸
• [Presentation] Viral non-self RNA in detected by RIG-I-like receptors in cytoplasmic granules (2011)
  • Author(s): Yoneyama M
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ,千葉(招待講演)
  • Year and Date: 2011-11-27
• [Presentation] Subcellular localization of RIG-Hike receptors in virus-infected cells (2011)
  • Author(s): Yoneyama M, Onomoto K, Jogi M, Fujita T
  • Organizer: 9^<th> Joint Meeting of International Cytokine Society and International Society for Interferon and Cytokine Research
  • Place of Presentation: Florence, Italy
  • Year and Date: 2011-10-10
• [Presentation] Granular-like accumulation of RIG-I-like receptors in virus-infected cells (2011)
  • Author(s): Jogi M, Onomoto K, Fujita T, Yoneyama M
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター,札幌
  • Year and Date: 2011-09-15
• [Presentation] Detection of viral non-self RNA by RIG-I-like receptors in cytoplasmic granule-like structure (2011)
  • Author(s): Yoneyama M, Onomoto K, Jogi M, Fujita T
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学,札幌(招待講演)
  • Year and Date: 2011-06-29
• [Presentation] Formation of granule-like structure in detection of viral non-self RNA by RIG-I-like receptors (2011)
  • Author(s): Yoneyama M, Onomoto K, Jogi M, Fujita T
  • Organizer: The 16^<th> Annual Meeting of the RNA Society and The 13^<th> Annual meeting of the RNA Society of Japan
  • Place of Presentation: 京都国際会館,京都
  • Year and Date: 2011-06-18
• [Presentation] Analysis of intracellular localization of viral RNA sensor (2011)
  • Author(s): Onomoto K, Yoneyama M, Fujita T
  • Organizer: Experimental Biology 2011 (Joint Meeting of AAA, AOS, ASBMB, ASIP, ASN and ASPET)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2011-04-09
• [Remarks] 千葉大学真菌医学研究センター感染免疫分野ホームページ
  • URL: http://www.pf.chiba-u.ac.jp/bunya_kansenmeneki/
• [Remarks] 千葉大学真菌医学研究センターホームページ
  • URL: http://www.pf.chiba-u.ac.jp/index.html
• [Remarks] 千葉大学真菌医学研究センター感染免疫分野
  • URL: http://www.pf.chiba-u.ac.jp/bunya_kansenmeneki/bunya_kansenmeneki/Mol._Immunol._jpn.html
• [Remarks]
  • URL: http://www.pf.chiba-u.ac.jp/bunya_kansenmeneki/bunya_kansenmeneki/Mol._Immunol._jpn.html