Molecular mechanism of viral RNP recognition by RIG-I-like receptors

• Project/Area Number: 26293101
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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)
• Co-Investigator(Kenkyū-buntansha): 西城 忍 千葉大学, 真菌医学研究センター, 准教授 (60396877)
• Co-Investigator(Renkei-kenkyūsha): ONOMOTO Koji 千葉大学, 真菌医学研究センター, 助教 (10612202)
• Research Collaborator: JOGI Michihiko
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: ウイルス / 免疫学 / 核酸 / RNA結合タンパク質 / RNA結合蛋白質 / 自然免疫

Outline of Final Research Achievements

In order to understand how viral RNA sensors, RIG-I-like receptors (RLRs), recognize viral ribonucleoprotein complexes (RNPs) in virus-infected cells, we assessed activation of RIG-I-mediated signaling by viral RNPs using in vitro reconstitution assay system. As a model RNPs, we prepared artificial RNPs of influenza A virus (IAV). In vitro assay indicated that RIG-I-mediated signaling is activated by IAV RNPs, however the data also suggest that host factor(s) is required for full-activation of the signal. The observations would help us to reveal a molecular machinery of activation of anti-viral innate immune responses.

Research Products

• [Journal Article] Regulation of antiviral innate immune signaling by stress-induced RNA granules. (2016)
  • Author(s): Yoneyama M, Jogi M, Onomoto K.
  • Journal Title: The Journal of Biochemistry Volume: 159 Pages: 279-286
  • DOI: 10.1093/jb/mvv122
  • NAID: 40020763323
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules. (2016)
  • Author(s): Oh SW, Onomoto K, Wakimoto M, Onoguchi K, Ishidate F, Fujiwara T, Yoneyama M, Kato H, Fujita T.
  • Journal Title: PLoS Pathogens Volume: 12 Issue: 2 Pages: 1-22
  • DOI: 10.1371/journal.ppat.1005444
  • NAID: 120005763384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Viral RNA detection by RIG-I-like receptors. (2015)
  • Author(s): Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T.
  • Journal Title: Curr. Opin. Immunol. Volume: 32 Pages: 48-53
  • DOI: 10.1016/j.coi.2014.12.012
  • Peer Reviewed / Acknowledgement Compliant
• [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
• [Presentation] Viral infection and anti-viral innate immune responses in animal cells (2017)
  • Author(s): Mitsutoshi Yoneyama
  • Organizer: 第58回日本植物生理学会年会
  • Place of Presentation: 鹿児島大学郡元キャンパス（鹿児島県・鹿児島市）
  • Year and Date: 2017-03-16
  • Invited
• [Presentation] Identification of a novel RNA binding protein that is involved in RLR-meriated signalingovel RNA binding protein that is involved in RLR-meriated signalingo (2016)
  • Author(s): Marie Ban, Koji Onomoto, Mitsutoshi Yoneyama
  • Organizer: The 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県・淡路市）
  • Year and Date: 2016-09-06
  • Int'l Joint Research
• [Presentation] ウイルス感染に応答したストレス顆粒形成と抗ウイルス生体防御 (2015)
  • Author(s): 米山光俊
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] RNAサイレンシングと抗ウイルス応答のクロストーク機構の解析 (2015)
  • Author(s): 中野悠子、高橋朋子、尾野本浩司、米山光俊、程久美子
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Regulation of anti-viral innate immunity by host RNA-binding proteins. (2015)
  • Author(s): Yoneyama, M.
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2015-11-22
  • Invited
• [Presentation] Molecular machinery of viral RNA recognition by RIG-I-like receptors. (2015)
  • Author(s): Yoneyama, M.
  • Organizer: 13th IGAKUKEN International Symposium on ”Molecular Basis of Viral Disease”
  • Place of Presentation: 東京都医学総合研究所（東京都・世田谷区）
  • Year and Date: 2015-11-20
  • Int'l Joint Research / Invited
• [Presentation] Regulation of antiviral innate immunity by the 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
• [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/project_immuneresponses/
• [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