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Identification and characterization of novel influenza A virus proteins

Research Project

Project/Area Number 26460549
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionThe University of Tokyo

Principal Investigator

Yamayoshi Seiya  東京大学, 医科学研究所, 特任准教授 (50529534)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsインフルエンザウイルス / PB2分節 / スプライス / 新規ウイルス蛋白質 / スプライシング / PB2
Outline of Final Research Achievements

Over the past two decades, several novel influenza viral proteins have been identified that modulate viral infections in vitro and/or in vivo. We used RT-PCR targeting viral mRNAs transcribed from the PB2 segment to look for novel viral proteins encoded by spliced mRNAs. We identified a new viral protein, termed PB2-S1, encoded by a novel spliced mRNA. PB2-S1 was detected in virus-infected cells and in cells transfected with a plasmid encoding PB2. PB2-S1 localized to mitochondria, inhibited the RIG-I-dependent interferon signaling pathway, and interfered with viral polymerase activity depending on its PB1 binding capability. The nucleotide sequences around the splicing donor and acceptor sites for PB2-S1 were highly conserved among human pre-2009 H1N1 viruses but not among human H1N1pdm and H3N2 viruses. PB2-S1-deficient viruses, however, showed similar growth kinetics in MDCK cells and virulence in mice to those of wild-type virus.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (15 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Evaluation of seasonal influenza vaccinese for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus.2017

    • Author(s)
      Ui H, Yamayoshi S, Uraki R, Kiso M, Oishi K, Murakami S, Mimori S, Kawaoka Y.
    • Journal Title

      Vaccine

      Volume: 4;35(15) Issue: 15 Pages: 1892-1897

    • DOI

      10.1016/j.vaccine.2017.02.041

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The host protein CLUH participates in the subnuclear transport of influenza virus ribonucleoprotein complexes2016

    • Author(s)
      Ando T, Yamayoshi S, Tomita Y, Watanabe T, Watanabe S, Kawaoka Y
    • Journal Title

      Nature Microbiology

      Volume: 1 Issue: 8 Pages: 16062-16062

    • DOI

      10.1038/nmicrobiol.2016.62

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk assessment of recent Egyptian H5N1 influenza viruses2016

    • Author(s)
      Arafa AS, Yamada S, Imai M, Watanabe T et al
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 38388-38388

    • DOI

      10.1038/srep38388

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Microminipig as an Animal Model for Influenza A Virus Infection2016

    • Author(s)
      Iwatsuki-Horimoto K, Nakajima N, Shibata M, Takahashi K, Sato Y, Kiso M, Yamayoshi S, Ito M, Enya S, Otake M, Kangawa A, da Silva Lopes TJ, Ito H, Hasegawa H, Kawaoka Y.
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 2 Pages: 1-9

    • DOI

      10.1128/jvi.01716-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A Broadly Reactive Human Anti-hemagglutinin Stem Monoclonal Antibody That Inhibits Influenza A Virus Particle Release.2016

    • Author(s)
      Yamayoshi S, Uraki R, Ito M, Kiso M, Nakatsu S, Yasuhara A, Oishi K, Sasaki T, Ikuta K,Kawaoka Y.
    • Journal Title

      EBioMedicine

      Volume: 17 Pages: 182-191

    • DOI

      10.1016/j.ebiom.2017.03.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Viral Protein Expressed from the PB2 Segment of Influenza A Virus.2016

    • Author(s)
      Yamayoshi S, Watanabe M, Goto H, Kawaoka Y.
    • Journal Title

      Journal of Virology

      Volume: 90 Issue: 1 Pages: 444-456

    • DOI

      10.1128/jvi.02175-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Amino acids substitutions in the PB2 protein of H7N9 influenza A viruses are important for virulence in mammalian hosts.2015

    • Author(s)
      Yamayoshi S, Fukuyama S, Yamada S, Zhao D, Murakami S, Uraki R, Watanabe T, Tomita Y, Neumann G, Kawaoka Y.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 8039-8039

    • DOI

      10.1038/srep08039

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel function site in the PB2 subunit of influenza A virus essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication.2014

    • Author(s)
      Hatkeyama D, Shoji M, Yamayoshi S, Hirota T, Nagae M, Yanagisawa S, Nakano M, Ohmi N, Noda T, Kawaoka Y, Kuzuhara T.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 36 Pages: 24980-94

    • DOI

      10.1074/jbc.m114.559708

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Virulence-Affecting Amino Acid Changes in the PA Protein of H7N9 Influenza A Viruses.2014

    • Author(s)
      Yamayoshi S, Yamada S, Fukuyama S, Murakami S, Zhao D, Uraki R, Watanabe T, Tomita Y, Macken C, Neumann G, Kawaoka Y
    • Journal Title

      Journal of Virology

      Volume: 88(6) Issue: 6 Pages: 3127-34

    • DOI

      10.1128/jvi.03155-13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] A broadly reactive human anti-hemagglutinin stem monoclonal antibody that inhibits influenza A virus particle release2017

    • Author(s)
      Yamayoshi S, Uraki R, Ito M, Kiso M, Nakatsu S, Yasuhara A, Oishi K, Sasaki T, Ikuta K, Kawaoka Y.
    • Organizer
      The 6th China‐Japan Bilateral Symposium on All Influenza virus
    • Place of Presentation
      中国・北京
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A broadly reactive human anti-HA monoclonal antibody that inhibits influenza A virus particle release2016

    • Author(s)
      S. Yamayoshi, R. Uraki, M. Ito, M. Kiso, S. Nakatsu, K. Oishi, A. Yasuhara, T. Sasaki, K. Ikuta, Y. Kawaoka
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Acetylation of NP of influenza virus affects viral transcription activities2016

    • Author(s)
      D. Hatakeyama, M. Shoji, S. Yamaysohi, R. Yho, N. Ohmi, S. Takenaka, Y. Arakaki, A. Masuda, T. Komatsu, A. Saitoh, M. Nakano, T. Noda, Y. Kawaoka, T. Kuzuhara
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of the regulatory mechanisms of the subnuclear transport of influenza progeny ribonucleoprotein complexes2016

    • Author(s)
      T. Ando, S. Yamaysohi, Y. Tomita, S. Watanabe, T. Watanabe, Y. Kawaoka
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Toward the identification of host proteins involved in the shutoff activity of influenza A virus PA-X2016

    • Author(s)
      K. Oishi, S. Yamayoshi, Y. Kawaoka
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Characterization of the antigenic properties of influenza A(H1N1)pdm09 virus2016

    • Author(s)
      A. Yasuhara, S. Yamayoshi, M. Ito, R. Uraki, S. Nakatsu, K. Oishi, P. Soni, T. Takenaga, C. Kawakami, E. Takashita, T. Sasaki, K. Ikuta, S. Yamada, Y. Kawaoka
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Involvement of CLUH in the subnuclear transport of influenza progeny ribonucleoprotein complexes2016

    • Author(s)
      T. Ando, S. Yamayoshi, S. Watanabe, T. Watanabe, Y. Kawaoka
    • Organizer
      The Options IX for the Control of Influenza
    • Place of Presentation
      アメリカ・シカゴ
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A broadly reactive human anti-HA monoclonal antibody that inhibits influenza A virus particle release2016

    • Author(s)
      S. Yamayoshi, R. Uraki, M. Ito, M. Kiso, S. Nakatsu, K. Oishi, A. Yasuhara, T. Sasaki, K. Ikuta, Y. Kawaoka
    • Organizer
      The Options IX for the Control of Influenza
    • Place of Presentation
      アメリカ・シカゴ
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Toward the identification of host proteins involved in the shutoff activity of influenza A virus PA-X2016

    • Author(s)
      K. Oishi, S. Yamayoshi, Y. Kawaoka
    • Organizer
      The Options IX for the Control of Influenza
    • Place of Presentation
      アメリカ・シカゴ
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of the antigenic properties of influenza A(H1N1)pdm09 virus2016

    • Author(s)
      A. Yasuhara, S. Yamayoshi, M. Ito, R. Uraki, S. Nakatsu, K. Oishi, P. Soni, T. Takenaga, T. Sasaki, K. Ikuta, S. Yamada, Y. Kawaoka
    • Organizer
      The Options IX for the Control of Influenza
    • Place of Presentation
      アメリカ・シカゴ
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of a novel viral protein expressed from the PB2 segment of influenza A virus2015

    • Author(s)
      S. Yamayoshi, M. Watanabe, H. Goto, M. Hatta, Y. Kawaoka
    • Organizer
      16th Negative Strand Virus Meeting 2015
    • Place of Presentation
      イタリア・シエナ
    • Year and Date
      2015-06-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A 型インフルンザウイルスが発現するPA_X の蛋白質発現抑制に重要な領域の同定2014

    • Author(s)
      大石康平、山吉誠也、河岡義裕
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-10
    • Related Report
      2014 Research-status Report
  • [Presentation] H7N9鳥インフルエンザウイルスのPB2蛋白質の627Kおよび701Dは哺乳類に対する高病原性に寄与する2014

    • Author(s)
      山吉誠也、福山聡、山田晋弥、Dongming Zhao、村上晋、浦木隆太、渡辺登喜子、百瀬(冨田) 有里子、Gabriele Neumann、河岡義裕
    • Organizer
      第157回 日本獣医学会学術集会
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of a novel viral protein expressed from the PB2 segment of influenza A virus2014

    • Author(s)
      S. Yamayoshi, M. Watanabe, R. Uraki, H. Goto, and Y. Kawaoka
    • Organizer
      16th International Congress of Virology
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2014-07-28
    • Related Report
      2014 Research-status Report
  • [Presentation] ウイルス増殖能に対するPB2 サブユニットにおける新規機能部位VRG 配列の役割2014

    • Author(s)
      畠山 大、庄司正樹、山吉誠也、廣田丈典、長江萌菜美、柳澤 伸、河岡義裕、葛原 隆
    • Organizer
      第28回インフルエンザ研究者交流の会シンポジウム
    • Place of Presentation
      鳥取市総合福祉センター(鳥取県鳥取市)
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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