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Roles of the hemagglutinin in pathogenicity of influenza virus

Research Project

Project/Area Number 25450422
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Veterinary medical science
Research InstitutionThe University of Tokyo

Principal Investigator

Watanabe Tokiko  東京大学, 医科学研究所, 特任准教授 (60557479)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsインフルエンザウイルス / ヘマグルチニン / 病原性 / スペイン風邪 / レセプター特異性 / 飛沫伝播性 / 宿主因子 / 宿主応答
Outline of Final Research Achievements

The 1918 pandemic influenza virus caused fatal pneumonia and an estimated 20-50 million deaths worldwide. To understand roles of the HA gene in efficient replication and high virulence of the 1918 virus, we examined the biological properties of reassortant viruses between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001; K173) in a mouse model. In addition to the 1918 HA, we demonstrated the role of viral RNA replication complex in efficient replication of viruses in mouse lungs, whereas only HA gene is responsible for lethality in mice. Increased expression of genes associated with the acute phase response and protein ubiquitination pathway were enriched during 1918 and 1918HA/K173 infections. These data suggest HA and the viral RNA polymerase complex are critical determinants of 1918 influenza pathogenesis, but only HA is responsible for extreme host responses observed in mice infected with the 1918 influenza virus.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (37 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 13 results)

  • [Int'l Joint Research] ウイスコンシン大学(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.2016

    • Author(s)
      Moncla LH, Zhong G, Nelson CW, Dinis JM, Mutschler J, Hughes AL, Watanabe T, Kawaoka Y, Friedrich TC
    • Journal Title

      Cell Host and Microbe

      Volume: 19 Issue: 2 Pages: 169-180

    • DOI

      10.1016/j.chom.2016.01.011

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] エボラワクチン開発研究の最前線2016

    • Author(s)
      渡辺登喜子、河岡義裕
    • Journal Title

      細胞工学

      Volume: 35 Pages: 247-251

    • NAID

      40020761371

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Identification of Stabilizing Mutations in an H5 HA Influenza Virus Protein.2015

    • Author(s)
      Hanson A, Imai M, Hatta M, McBride R, Imai H, Taft A, Zhong G, Watanabe T, Suzuki Y, Neumann G, Paulson JC, Kawaoka Y.
    • Journal Title

      Journal of Virology

      Volume: 90 Issue: 6 Pages: 2981-2990

    • DOI

      10.1128/jvi.02790-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The 1918 PB2 protein enhances virulence through the disruption of inflammatory and Wnt-mediated signaling in mice.2015

    • Author(s)
      Forero A, Tisoncik-Go J, Watanabe T, Zhong G, Hatta M, Tchitchek N, Selinger C, Chang J, Barker K, Morrison J, Berndt JD, Moon RT, Josset L, Kawaoka Y, Katze MG.
    • Journal Title

      Journal of Virology

      Volume: 90 Issue: 5 Pages: 2240-2253

    • DOI

      10.1128/jvi.02974-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation.2015

    • Author(s)
      Shoemaker JE, Fukuyama S, Eisfeld AJ, Zhao D, Kawakami E, Sakabe S, Maemura T, Gorai T, Katsura H, Muramoto Y, Watanabe S, Watanabe T, Fuji K, Matsuoka Y, Kitano H, Kawaoka Y
    • Journal Title

      PLoS Pathogens

      Volume: 11 Issue: 6 Pages: e1004856-e1004856

    • DOI

      10.1371/journal.ppat.1004856

    • NAID

      120006987004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Influenza virus-host interactomes as a basis for antiviral drug development.2015

    • Author(s)
      Watanabe T, Kawaoka Y
    • Journal Title

      Current Opinion of Virology

      Volume: 14 Pages: 71-78

    • DOI

      10.1016/j.coviro.2015.08.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] インフルエンザウイルスの感染動物モデル~フェレット編~2015

    • Author(s)
      渡辺登喜子
    • Journal Title

      実験動物感染症と感染症動物モデルの現状

      Volume: 1 Pages: 123-1287

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Influenza virus-host interactome screen as a platform for antiviral drug development.2014

    • Author(s)
      Watanabe T, Kawakami E, Shoemaker JE, Lopes TJ, Matsuoka Y, Tomita Y, Kozuka-Hata H, Gorai T, Kuwahara T, Takeda E, Nagata A, Takano R, Kiso M, Yamashita M, Sakai-Tagawa Y, Katsura H, Nonaka N, Fujii H, Fujii K, Sugita Y, Noda T, Goto H, Fukuyama S, Watanabe S, Neumann G, Oyama M, Kitano H, Kawaoka Y.
    • Journal Title

      Cell Host and Microbe

      Volume: 16 Issue: 6 Pages: 795-805

    • DOI

      10.1016/j.chom.2014.11.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential.2014

    • Author(s)
      Watanabe T, Zhong G, Russell CA, Nakajima N, Hatta M, Hanson A, McBride R, Burke DF, Takahashi K, Fukuyama S, Tomita Y, Maher EA, Watanabe S, Imai M, Neumann G, Hasegawa H, Paulson JC, Smith DJ, Kawaoka Y
    • Journal Title

      Cell Host and Microbe

      Volume: 15 Issue: 6 Pages: 692-705

    • DOI

      10.1016/j.chom.2014.05.006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pandemic potential of avian influenza A (H7N9) viruses.2014

    • Author(s)
      Watanabe T, Watanabe S, Maher EA, Neumann G, Kawaoka Y
    • Journal Title

      Trends in Microbiology

      Volume: 22 Issue: 11 Pages: 623-31

    • DOI

      10.1016/j.tim.2014.08.008

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 中国で発生した鳥インフルエンザA(H7N9)について2014

    • Author(s)
      渡辺登喜子、河岡義裕
    • Journal Title

      カレントテラピー

      Volume: 32 Pages: 50-55

    • Related Report
      2013 Research-status Report
  • [Journal Article] Virulence determinants of pandemic A(H1N1)2009 influenza virus in a mouse model2013

    • Author(s)
      Uraki R, Kiso M, Shinya K, Goto H, Takano R, Iwatsuki-Horimoto K, Takahashi K, Daniels RS, Hungnes O, Watanabe T, Kawaoka Y.
    • Journal Title

      Journal of Virology

      Volume: 87(4) Issue: 4 Pages: 2226-2233

    • DOI

      10.1128/jvi.01565-12

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 1918 Influenza virus hemagglutinin (HA) and the viral RNA polymerase complex enhance viral pathogenicity, but only HA induces aberrant host responses in mice.2013

    • Author(s)
      Watanabe T, Tisoncik-Go J, Tchitchek N, Watanabe S, Benecke AG, Katze MG, Kawaoka Y
    • Journal Title

      Journal f Virology

      Volume: 87 Issue: 9 Pages: 5239-5254

    • DOI

      10.1128/jvi.02753-12

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of H7N9 influenza A viruses isolated from humans.2013

    • Author(s)
      Watanabe T, Kiso M, Fukuyama S, Nakajima N, Imai M, Yamada S, Murakami S, Yamayoshi S, Iwatsuki-Horimoto K, Sakoda Y, Takashita E, McBride R, Noda T, Hatta M, Imai H, Zhao D, Kishida N, Shirakura M, de Vries RP, Shichinohe S, Okamatsu M, Tamura T, Tomita Y , Fujimoto N, Goto K, Katsura H, Kawakami E, Ishikawa I, Watanabe S, Ito M, Sakai-Tagawa Y, Sugita Y, Uraki R, Yamaji R, Eisfeld AJ, Zhong G, Fan S, Ping J, Maher EA, Hanson A, Uchida Y, Saito T, Ozawa M, Neumann G, Kida H, Odagiri T, Paulson JC, Hasegawa H, Tashiro M, Kawaoka Y
    • Journal Title

      Nature

      Volume: 501(7468) Issue: 7468 Pages: 551-5

    • DOI

      10.1038/nature12392

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A comprehensive map of the influenza A virus replication cycle.2013

    • Author(s)
      Matsuoka Y, Matsumae H, Katoh M, Eisfeld AJ, Neumann G, Hase T, Ghosh S, Shoemaker JE, Lopes TJ, Watanabe T, Watanabe S, Fukuyama S, Kitano H, Kawaoka Y.
    • Journal Title

      BMC Systems Biology

      Volume: 7 Issue: 1 Pages: 97-97

    • DOI

      10.1186/1752-0509-7-97

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] H5N1鳥インフルエンザウイルスはヒトで流行するか?2013

    • Author(s)
      渡辺登喜子、渡邉真治、河岡義裕
    • Journal Title

      日本内科学会雑誌

      Volume: 102 Pages: 2705-2713

    • NAID

      130004696818

    • Related Report
      2013 Research-status Report
  • [Journal Article] 鳥インフルエンザウイルスパンデミックの恐怖2013

    • Author(s)
      渡辺登喜子、河岡義裕
    • Journal Title

      実験医学

      Volume: 31 Pages: 3040-3046

    • Related Report
      2013 Research-status Report
  • [Presentation] Host-virus interactions in influenza virus replication2015

    • Author(s)
      Tokiko Watanabe
    • Organizer
      The 14th 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
      2015-09-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of host factors involved in influenza virus replication2015

    • Author(s)
      Tokiko Watanabe, Eiryo Kawakami, Jason E. Shoemaker, Tiago J. S. Lopes, Yukiko Matsuoka, Yuriko Tomita, Hiroko Kozuka-Hata, Shinji Watanabe, Masaaki Oyama, Hiroaki Kitano, Yoshihiro Kawaoka
    • Organizer
      Negative strand virus meeting 2015
    • Place of Presentation
      Siena, Italy
    • Year and Date
      2015-06-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルス感染における宿主因子の役割2015

    • Author(s)
      渡辺登喜子
    • Organizer
      第29回インフルエンザ研究者交流の会
    • Place of Presentation
      東京大学医科学研究所(東京都港区)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] インフルエンザウイルスの病原性発現機構の解析2015

    • Author(s)
      渡辺登喜子
    • Organizer
      大阪大学微生物病研究所
    • Place of Presentation
      大阪大学微生物研究所
    • Year and Date
      2015-02-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] インフルエンザウイルス増殖に関わる宿主因子の同定 ~抗ウイルス薬開発への応用~2014

    • Author(s)
      渡辺登喜子
    • Organizer
      第4回バイオガレージセミナー~RNAウイルス研究の最前線~
    • Place of Presentation
      株式会社リバネス(東京都)
    • Year and Date
      2014-12-16
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] スペイン風邪ウイルスに類似の鳥インフルエンザウイルスのパンデミックポテンシャル2014

    • Author(s)
      渡辺登喜子、Gongxun Zhong, Colin A. Russell, 中島典子、八田正人、Anthony Hanson,高橋健太、渡辺真治、今井正樹、長谷川秀樹、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
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 鳥インフルエンザウイルスパンデミックの可能性.2014

    • Author(s)
      渡辺登喜子
    • Organizer
      生理学研究所一般公開
    • Place of Presentation
      生理学研究所(岡崎市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 中国における人のH7N9亜型鳥インフルエンザウイルス感染の現状2014

    • Author(s)
      渡辺登喜子
    • Organizer
      第157回獣医学会学術集会
    • Place of Presentation
      北海道大学
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] インフルエンザA(H7N9)ウイルスの性状について.2014

    • Author(s)
      渡辺登喜子
    • Organizer
      衛生微生物技術協議会第35回研究会
    • Place of Presentation
      東京都江戸川区船堀 タワーホール船堀
    • Year and Date
      2014-06-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] インフルエンザウイルスの感染動物モデル~フェレット編~2014

    • Author(s)
      渡辺登喜子
    • Organizer
      第61回日本実験動物科学技術さっぽろ2014
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2014-05-14 – 2014-05-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Pandemic Potential of H7N9 influenza A Viruses Isolated from Humans2014

    • Author(s)
      Tokiko Watanabe
    • Organizer
      新興・再興感染症に関するアジア・アフリカリサーチフォーラム
    • Place of Presentation
      仙台国際センター(仙台市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 中国でヒトから分離されたH7N9鳥インフルエンザウイルスについて2013

    • Author(s)
      渡辺 登喜子
    • Organizer
      第27回インフルエンザ研究者交流の会シンポジウム
    • Place of Presentation
      北海道大学獣医学研究科(札幌市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 中国で分離されたH7N9鳥インフルエンザウイルスのフェレットにおける飛沫伝播性.2013

    • Author(s)
      渡辺登喜子、今井博貴、村上晋、中島典子、冨田有里子、山吉誠也、浦木隆太、西藤岳彦、内田裕子、長谷川秀樹、田代眞人、河岡義裕
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 鳥インフルエンザウイルスの脅威2013

    • Author(s)
      渡辺 登喜子
    • Organizer
      第2回NINS Colloquium (自然科学研究機構)
    • Place of Presentation
      ヤマハリゾートつま恋(静岡県掛川市満水)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 昨今のインフルエンザ事情

    • Author(s)
      渡辺 登喜子
    • Organizer
      福岡呼吸器アーベント
    • Place of Presentation
      ホテルレオパレス博多(博多市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] H7N9インフルエンザウイルスについて

    • Author(s)
      渡辺 登喜子
    • Organizer
      第1回バイオセキュリティワークショップ
    • Place of Presentation
      慶応大学(東京都港区三田)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] インフルエンザ感染における宿主因子の役割

    • Author(s)
      渡辺 登喜子
    • Organizer
      インフルエンザを制圧する
    • Place of Presentation
      東京大学医科学研究所(東京都港区白金台)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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