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The quality control of viral particles through the endocytic transport of viral genome

Research Project

Project/Area Number 18K07137
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Fukuda Mikako  筑波大学, 医学医療系, 研究員 (60814655)

Co-Investigator(Kenkyū-buntansha) 川口 敦史  筑波大学, 医学医療系, 教授 (90532060)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsウイルス粒子形成 / インフルエンザ / 粒子形成 / 脂質ラフト
Outline of Final Research Achievements

After the nuclear export, the replicated viral genome is transported to the plasma membrane via Rab11a-positive transport vesicles in a microtubule-dependent manner. We found that inhibition of the vesicular transport system reduced the density of viral membrane proteins on viral particles, and that ARHGAP1 on Rab11a-positive transport vesicles promotes the clustering of viral membrane proteins in concert with viral genome transport. The clustering of lipid rafts in response to the viral genome trafficking results in the formation of "high-quality" viral particles with spike viral proteins. This is an important strategy not only for achieving stability of viral particles in the external environment, but also for evading the host immune system.

Academic Significance and Societal Importance of the Research Achievements

これまで、細胞膜上でのウイルス粒子形成機構については、十分な観察技術が無く、ほとんど明らかにされていなかった。本研究では、高解像度・高時間分解能で細胞膜上でのウイルス粒子形成を観察する技術を開発することで、ウイルスゲノムの細胞膜への輸送に協調して、ウイルス膜タンパク質が集積する分子機構を解析した。特に、アクチンフィラメントを介したウイルス膜タンパク質の流動性の制御により、ウイルス粒子の質が決定されることを明らかにした。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Remarks (1 results)

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

    • Related Report
      2019 Research-status Report
  • [Journal Article] ARHGAP1 transported with influenza viral genome ensures integrity of viral particle surface through efficient budozone formation.2022

    • Author(s)
      Kuroki T, Hatta T, Natsume T, Sakai N, Yagi A, Kato K, Nagata K, Kawaguchi A.
    • Journal Title

      mBio

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent mouse monoclonal antibodies that block SARS-CoV-2 infection2021

    • Author(s)
      Guo Youjia、Kawaguchi Atsushi、Takeshita Masaru、Sekiya Takeshi、Hirohama Mikako、Yamashita Akio、Siomi Haruhiko、Murano Kensaku
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100346-100346

    • DOI

      10.1016/j.jbc.2021.100346

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents2021

    • Author(s)
      Konno S、Kobayashi K、Senda M、Funai Y、Seki Y、Tamai I、Schakel L、Sakata K、Pillaiyar T、Taguchi A、Taniguchi A、Gutschow M、Muller CE.、Takeuchi K、Hirohama M、Kawaguchi A、Kojima M、Senda T、Shirasaka Y、Kamitani W、Hayashi Y
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 65 Issue: 4 Pages: 2926-2939

    • DOI

      10.1021/acs.jmedchem.1c00665

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interaction of influenza A virus NS2/NEP protein with the amino-terminal part of Nup2142020

    • Author(s)
      SENBAS AKYAZI Burcak、PIRINCAL Aysegul、KAWAGUCHI Atsushi、NAGATA Kyosuke、TURAN Kadir
    • Journal Title

      TURKISH JOURNAL OF BIOLOGY

      Volume: 44 Issue: 2 Pages: 82-92

    • DOI

      10.3906/biy-1909-49

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influenza restriction factor MxA functions as inflammasome sensor in the respiratory epithelium2019

    • Author(s)
      Lee SangJoon、Ishitsuka Akari、Noguchi Masayuki、Hirohama Mikako、Fujiyasu Yuji、Petric Philipp P.、Schwemmle Martin、Staeheli Peter、Nagata Kyosuke、Kawaguchi Atsushi
    • Journal Title

      Science Immunology

      Volume: 4 Issue: 40

    • DOI

      10.1126/sciimmunol.aau4643

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed
  • [Presentation] インフルエンザウイルス感染に対するMxAインフラマソームによる気道上皮組織炎症応答2021

    • Author(s)
      川口敦史
    • Organizer
      第34回インフルエンザ研究者交流の会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 濃厚接触者を対象にしたSARS-CoV-2の感染性を決定するSNP変異の探索2021

    • Author(s)
      関屋健史, 甲斐平康, 山縣邦弘, 広浜美香子, 大川詩乃, 川口敦史
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂質キナーゼPI5P4K依存的なインフルエンザウイルスとコロナウイルスの初期増殖機構2021

    • Author(s)
      國本航平, 黒木崇央, 竹内恒, 川口敦史
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] SARS-CoV-2感染における性差の化学遺伝学的な解析2021

    • Author(s)
      大川詩乃, Mojica Aileen, 川口敦史
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Influenza viral budozone formation in concert with vesicular transport of viral genome ensures functional integrity of virions for immune evasion2021

    • Author(s)
      Takahiro Kuroki, Kohsuke Kato, Kyosuke Nagata, Atsushi Kawaguchi
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] インフルエンザウイルス感染による気道上皮組織の炎症応答機構2020

    • Author(s)
      川口敦史
    • Organizer
      第94回日本感染症学会総会・学術講演会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Regulatory mechanism of respiratory epithelium-specific inflammatory response upon influenza virus infection by a novel NS1 binding protein2019

    • Author(s)
      Takeshi Sekiya, Mikako Hirohama, Atsushi Kawaguchi
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [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 Research-status Report
    • Invited
  • [Presentation] Molecular mechanism of host responses against influenza virus infection2019

    • Author(s)
      Kawaguchi A.
    • Organizer
      Infectious disease symposium
    • Related Report
      2018 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
    • 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 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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