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Respiratory epithelium-specific inflammatory response against influenza virus infection

Research Project

Project/Area Number 16H05192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionUniversity of Tsukuba

Principal Investigator

Kawaguchi Atsushi  筑波大学, 医学医療系, 准教授 (90532060)

Co-Investigator(Kenkyū-buntansha) 夏目 徹  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究センター長 (00357683)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsインフルエンザウイルス / 炎症応答 / 気道上皮組織 / サイトカイン / 気道上皮細胞 / ウイルス / 感染症 / 炎症
Outline of Final Research Achievements

Respiratory epithelium functions as a first defender against infectious agents by separating the body from external environment and by initially producing inflammatory cytokines. As a result of the cytokine response, macrophages and neutrophils are migrated to the infected tissues to eliminate infectious agents. In this study, we analyzed the inflammatory response mechanism in respiratory epithelial cells and identified respiratory epithelium-specific inflammasome receptors. We also identified host factors that are utilized by influenza virus to evade the inflammatory response.

Academic Significance and Societal Importance of the Research Achievements

気道上皮組織における炎症応答は感染初期の生体防御に必須であるのに対し、過剰な炎症応答が誘導されることで、発熱や肺炎症状を引き起こす。本研究ではインフルエンザウイルス感染による炎症応答の誘導機構を宿主側及びウイルス側から明らかにし、ウイルス感染による病態発現機構の一部を明らかにすることができた。本研究成果は、今後、インフルエンザ重症例における治療方法の新規開拓へと繋がっていくと期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (44 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 8 results) Presentation (26 results) (of which Int'l Joint Research: 7 results,  Invited: 11 results) Remarks (2 results)

  • [Int'l Joint Research] フライブルグ大学(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] フライブルグ大学(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Involvement of CTCF in transcription regulation of EGR1 at early G1 phase as an architecture factor2019

    • Author(s)
      Sekiya Takeshi、Kato Kohsuke、Kawaguchi Atsushi、Nagata Kyosuke
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 329-329

    • DOI

      10.1038/s41598-018-36753-x

    • NAID

      120007128186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza A Virus NS1 Protein Suppresses JNK1-Dependent Autophagosome Formation Mediated by Rab11a Recycling Endosomes.2018

    • Author(s)
      Kuroki T, Osari S, Nagata K, Kawaguchi A.
    • Journal Title

      Frontiers in Microbiology

      Volume: 9 Pages: 3120-3120

    • DOI

      10.3389/fmicb.2018.03120

    • NAID

      120007133666

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Influenza Virus Infection by Lentinus edodes Mycelia Extract Through Its Direct Action and Immunopotentiating Activity.2018

    • Author(s)
      Kuroki T, Lee S, Hirohama M, Taku T, Kumakura M, Haruyama T, Nagata K, Kawaguchi A.
    • Journal Title

      Frontiers in Microbiology

      Volume: 9 Pages: 1164-1164

    • DOI

      10.3389/fmicb.2018.01164

    • NAID

      120007134009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner.2018

    • Author(s)
      Lee S, Hirohama M, Noguchi M, Nagata K, Kawaguchi A.
    • Journal Title

      Journal of Virology

      Volume: 92 Issue: 14

    • DOI

      10.1128/jvi.00396-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical characterization of avian influenza viral polymerase containing PA or PB2 subunit from human influenza A virus.2018

    • Author(s)
      Pham PTV, Turan K, Nagata K, Kawaguchi A.
    • Journal Title

      Microbes and Infection

      Volume: 20 Issue: 6 Pages: 353-359

    • DOI

      10.1016/j.micinf.2018.04.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stratifin regulates stabilization of receptor tyrosine kinases via interaction with ubiquitin-specific protease 8 in lung adenocarcinoma2018

    • Author(s)
      Kim Yunjung、Shiba-Ishii Aya、Nakagawa Tomoki、Iemura Shun-ichiro、Natsume Tohru、Nakano Noriyuki、Matsuoka Ryota、Sakashita Shingo、Lee SangJoon、Kawaguchi Atsushi、Sato Yukio、Noguchi Masayuki
    • Journal Title

      Oncogene

      Volume: 37 Issue: 40 Pages: 5387-5402

    • DOI

      10.1038/s41388-018-0342-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assembly and remodeling of viral DNA and RNA replicons regulated by cellular molecular chaperones2018

    • Author(s)
      Sekiya Takeshi、Hu Yifan、Kato Kohsuke、Okuwaki Mitsuru、Kawaguchi Atsushi、Nagata Kyosuke
    • Journal Title

      Biophys. Rev.

      Volume: 10 Issue: 2 Pages: 445-452

    • DOI

      10.1007/s12551-017-0333-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers2018

    • Author(s)
      Sakai Y, Kawaguchi A, Nagata K, Hirokawa T.
    • Journal Title

      Microbiolofy and Immunology

      Volume: 62(1) Issue: 1 Pages: 34-43

    • DOI

      10.1111/1348-0421.12561

    • NAID

      40021443646

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity2017

    • Author(s)
      Yoshizumi T, Imamura H, Taku T, Kuroki T, Kawaguchi A, Ishikawa K, Nakada K, Koshiba T
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 5379-5379

    • DOI

      10.1038/s41598-017-05808-w

    • NAID

      120007128833

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular splicing factor UAP56 stimulates trimeric NP formation for assembly of functional influenza viral ribonucleoprotein complexes2017

    • Author(s)
      Hu Yifan、Gor Vishal、Morikawa Kazuya、Nagata Kyosuke、Kawaguchi Atsushi
    • Journal Title

      Scientific Reports

      Volume: 7(1) Issue: 1 Pages: 14053-14053

    • DOI

      10.1038/s41598-017-13784-4

    • NAID

      120007134654

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] インフルエンザウイルスと核内構造2017

    • Author(s)
      1.黒木崇央、川口敦史
    • Journal Title

      生体の科学

      Volume: 68(3) Pages: 256-260

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity.2017

    • Author(s)
      Sekiya T, Murano K, Kato K, Kawaguchi A, Nagata K.
    • Journal Title

      FEBS Open Bio

      Volume: 7 Issue: 3 Pages: 397-404

    • DOI

      10.1002/2211-5463.12189

    • NAID

      120007129136

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity.2017

    • Author(s)
      Minakuchi M, Sugiyama K, Kato Y, Naito T, Okuwaki M, Kawaguchi A, Nagata K.
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 3

    • DOI

      10.1128/jvi.01398-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polycomb repressive complex 2 facilitates the nuclear export of the influenza viral genome through the interaction with M1.2016

    • Author(s)
      Asaka MN, Kawaguchi A, Sakai Y, Mori K, Nagata K.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 33608-33608

    • DOI

      10.1038/srep33608

    • NAID

      120007129419

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] インフルエンザウイルス感染に対する気道上皮組織特異的な炎症応答機構2019

    • Author(s)
      川口敦史
    • Organizer
      都医学研セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of host responses against influenza virus infection2019

    • Author(s)
      Kawaguchi A.
    • Organizer
      Infectious disease symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Respiratory epithelium-specific inflammasome restricts influenza A virus infection2019

    • Author(s)
      Kawaguchi A.
    • Organizer
      Symposium on influenza and other infections
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ウイルスポリメラーゼの動態構造から読み解く新型インフルエンザの Outbreak2019

    • Author(s)
      川口敦史
    • Organizer
      筑波大-KEK連携セミナーシリーズ 第5回
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Inhibition of type I IFN production in avian influenza virus-infected macrophages2018

    • Author(s)
      Kameyama K, Nagata K, Kawaguchi A.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Influenza virus NS1 protein inhibits selective autophagy induced by virus genome recognition2018

    • Author(s)
      Kuroki T, Osari S, Nagata K, Kawaguchi A.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Influenza virus restriction factor MxA functions as inflammasome receptor in respiratory epithelium2018

    • Author(s)
      Lee S, Nagata K, Kawaguchi A.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Influenza A virus infection induces apoptosis and pyroptosis in respiratory epithelial cells in a mutually exclusive manner2018

    • Author(s)
      Kawaguchi A.
    • Organizer
      Asian-Pacific Centenary Spanish 1918-flu Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多様なコンフォメーションの解析を可能にするクライオ電子顕微鏡解析2018

    • Author(s)
      岩崎憲治、川口敦史
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 構造生物学的解析とそれに基づく創薬2017

    • Author(s)
      川口敦史
    • Organizer
      TIAかけはしワークショップ 放射光利用における新分野開拓のための連携形成
    • Place of Presentation
      つくばイノベーションプラザ・茨城県・つくば
    • Year and Date
      2017-03-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Biochemical and structural analysis of capping reaction of influenza viral polymerase2017

    • Author(s)
      Kawaguchi A.
    • Organizer
      The Sixth China-Japan Bilateral Symposium on All Influenza Viruses
    • Place of Presentation
      Chinese Academy of Sciences・中国・北京
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 小胞輸送系を介したインフルエンザウイルスゲノムの細胞内動態制御機構2017

    • Author(s)
      川口敦史
    • Organizer
      東京大学医科学研究所共同研究拠点事業 平成28年度若手研究者シンポジウム
    • Place of Presentation
      東京大学医科学研究所・東京都・白金
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Novel role of ESIR inflammasome in respiratory epithelialcells during influenza A virus infection2017

    • Author(s)
      SangJoon Lee、川口敦史
    • Organizer
      第14回ウイルス学キャンプ in 湯河原
    • Related Report
      2017 Annual Research Report
  • [Presentation] インフルエンザウイルスゲノムの小胞媒介性輸送機構はウイルス膜タンパク質のアセンブリを促進する2017

    • Author(s)
      黒木崇央、永田恭介、川口敦史
    • Organizer
      第14回ウイルス学キャンプ in 湯河原
    • Related Report
      2017 Annual Research Report
  • [Presentation] クロマチン結合因子CTCFによるEGR1遺伝子のG1期初期における転写制御機構2017

    • Author(s)
      関屋健史、永田恭介、川口敦史
    • Organizer
      第14回ウイルス学キャンプ in 湯河原
    • Related Report
      2017 Annual Research Report
  • [Presentation] Recycling endosome-mediated influenza virus genome transport is required for the assembly of stable viral particles2017

    • Author(s)
      黒木崇央、永田恭介、川口敦史
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Intracellular Localization of phosphatidylinositol (4,5)-Bisphosphate is altered by influenza virus infection2017

    • Author(s)
      Vo Nguyen Dan Linh、永田恭介、川口敦史
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] インフルエンザウイルスの宿主域に関与する転写型ウイルスポリメラーゼの機能構造2017

    • Author(s)
      川口敦史
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 小胞輸送系を介したインフルエンザウイルス子孫RNP複合体の細胞内動態2016

    • Author(s)
      川口敦史
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜・神奈川県・横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Dynamics of the influenza virus genome regulated by cellular host factors.2016

    • Author(s)
      Kawaguchi A.
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター・北海道・札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Viral budozone formation in concert with influenza virus genome transport using recycling endosomes.2016

    • Author(s)
      Kuroki T, Nagata K, Kawaguchi A.
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター・北海道・札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In situ detection of M1-NS2 complex formation essential for nuclear export of the influenza virus genome.2016

    • Author(s)
      Yamashita S, Asaka MN, Nagata K, Kawaguchi A.
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター・北海道・札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Influenza A virus infection induces Caspase-1-dependent cell death with pro-inflammatory cytokines in human lung epithelial cells.2016

    • Author(s)
      Lee SJ, Nagata K, Kawaguchi A.
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター・北海道・札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルスvRNPの輸送の方向性を決定する分子機構2016

    • Author(s)
      原田芳美、川口敦史.
    • Organizer
      第13回ウイルス学キャンプ in 湯河原
    • Place of Presentation
      ニューウェルシティ湯河原・静岡県・熱海
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] CRM1によるインフルエンザウイルスの核外輸送複合体の形成機構2016

    • Author(s)
      山下俊、川口敦史.
    • Organizer
      第13回ウイルス学キャンプ in 湯河原
    • Place of Presentation
      ニューウェルシティ湯河原・静岡県・熱海
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] インフルエンザウイルスゲノムの細胞内輸送と協調したウイルス粒子形成機構2016

    • Author(s)
      黒木崇央、川口敦史
    • Organizer
      第13回ウイルス学キャンプ in 湯河原
    • Place of Presentation
      ニューウェルシティ湯河原・静岡県・熱海
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/virology/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 筑波大学医学医療系分子ウイルス学

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/virology/

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2023-03-16  

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