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MECHANISMS FOR REPLICATION OF MEASLES AND INFLUENZA VIRUSES IN POLARIZED EPITHELIAL CELLS

Research Project

Project/Area Number 20390133
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKyushu University

Principal Investigator

MAKOTO Takeda  Kyushu University, ウイルス第三部, 部長 (40311401)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords感染症 / ウイルス / 微生物 / 麻疹 / インフルエンザ / 極性上皮細胞 / 極性細胞
Research Abstract

Our aims in this study were identification of host factors for efficient replication of measles virus and influenza virus in epithelial cells. Previous studies have revealed that measles virus selectively infects cells of the immune system. However, we recently showed that epithelial cells that form tight junctions (polarized epithelial cells) were also susceptible to measles virus. The transcription repressor Snail causes epithelial-to-mesenchymal transition (EMT). When Snail was expressed, polarized epithelial cells lost the ability to support measles virus infection. Microarray analysis identified about 30 genes, whose expression levels were down-regulated by Snal-induced EMT. For influenza virus, cleavage of its HA protein was critical for replication. Recent studies showed that the transmembrane serine protease TMPRSS2 cleaves the HA protein. We showed that TMPRSS2 was expressed in polarized epithelial cells and supports influenza virus replication, and that its expression was down-regulated by Snail-induced EMT.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (59 results)

All 2010 2009 2008 Other

All Journal Article (21 results) (of which Peer Reviewed: 14 results) Presentation (26 results) Book (9 results) Remarks (3 results)

  • [Journal Article] Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus.2010

    • Author(s)
      Shirogane Y, Takeda M, Tahara M, Ikegame S, Nakamura T, Yanagi Y
    • Journal Title

      J Biol Chem. 27

      Pages: 20882-90

    • Related Report
      2010 Final Research Report
  • [Journal Article] The F gene of the osaka-2 strain of measles virus derived from a case of subacute sclerosing panencephalitis is a major determinant of neurovirulence.2010

    • Author(s)
      Ayata M, Takeuchi K, Takeda M, Ohgimoto S, Kato S, Sharma LB, Tanaka M, Kuwamura M, Ishida H, Ogura H
    • Journal Title

      J Virol. 84

      Pages: 11189-99

    • Related Report
      2010 Final Research Report
  • [Journal Article] Efficient activation of SARS coronavirus spike protein by the transmembrane protease, TMPRSS2.2010

    • Author(s)
      Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F
    • Journal Title

      J.Virol. 84

      Pages: 12658-64

    • Related Report
      2010 Final Research Report
  • [Journal Article] RIG-I and MDA5 RNA Helicases Both Contribute to the Induction of Interferon-{alpha}/{beta} in Measles Virus-Infected Human Cells.2010

    • Author(s)
      Ikegame, et al.
    • Journal Title

      Journal of Virology

      Volume: 84 Pages: 372-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus.2010

    • Author(s)
      Shirogane, et al.
    • Journal Title

      J Biol Chem

      Volume: 27 Pages: 20882-90

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient activation of SARS coronavirus spike protein by the transmembrane protease, TMPRSS2.2010

    • Author(s)
      Matsuyama, et al.
    • Journal Title

      Journal of Virology

      Volume: 84 Pages: 12658-64

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RIG-I and MDA5 RNA Helicases Both Contribute to the Induction of Interferon-{alpha}/{beta} in Measles Virus-Infected Human Cells2010

    • Author(s)
      Ikegame, et al.
    • Journal Title

      Journal of Virology 84

      Pages: 372-379

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteolytic activation of the 1918 influenza virus hemagglutinin.2009

    • Author(s)
      Chaipan C, Kobasa D, Bertram S, Glowacka I, Steffen I, Tsegaye TS, Takeda M, Bugge TH, Kim S, Park Y, Marzi A, Pohlmann S
    • Journal Title

      J Virol. 83

      Pages: 3200-11

    • Related Report
      2010 Final Research Report
  • [Journal Article] The matrix protein of measles virus regulates viral RNA synthesis and assembly by interacting with the nucleocapsid protein.2009

    • Author(s)
      Iwasaki M, Takeda M, Shirogane Y, Nakatsu Y, Nakamura T, Yanagi Y
    • Journal Title

      J Virol. 83

      Pages: 10374-10383

    • Related Report
      2010 Final Research Report
  • [Journal Article] A highly attenuated measles virus vaccine strain encodes a fully functional C protein.2009

    • Author(s)
      Nakatsu, et al.
    • Journal Title

      Journal of Virology 83

      Pages: 11996-12001

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitofusin 2 inhibits mitochondrial antiviral signaling2009

    • Author(s)
      Yasukawa, et al.
    • Journal Title

      Science Signaling 2

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The matrix protein of measles virus regulates viral RNA synthesis and assembly by interacting with the nucleocapsid protein2009

    • Author(s)
      Iwasaki, et al.
    • Journal Title

      Journal of Virology 83

      Pages: 10374-10383

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measles virus infects both polarized epithelial and immune cells using distinctive receptor-binding sites on its hemagglutinin.2008

    • Author(s)
      Tahara M, Takeda M, Shirogane Y, Hashiguchi T, Ohno S, Yanagi Y
    • Journal Title

      J Virol. 82

      Pages: 4630-4637

    • Related Report
      2010 Final Research Report
  • [Journal Article] Efficient Multiplication of Human Metapneumovirus in Vero Cells Expressing the Transmembrane Serine Protease TMPRSS2.2008

    • Author(s)
      Shirogane Y, Takeda M, Iwasaki M, Ishiguro, N, Takeuchi H, Nakatsu Y, Tahara M, Kikuta H, Yanagi Y
    • Journal Title

      J Virol. 82

      Pages: 8942-8946

    • Related Report
      2010 Final Research Report
  • [Journal Article] Measles virus infects both polarized epithelial and immune cells usingdistinctive receptor-binding sites on its hemagglutinin.2008

    • Author(s)
      Tahara, et al.
    • Journal Title

      Journal of Virology 82

      Pages: 4630-4637

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measles virus breaks through epithelial cell barriers to achieve transmisslon.2008

    • Author(s)
      Takeda
    • Journal Title

      Journal of Clinical Investigations 118

      Pages: 2386-2389

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homogeneous sugar modification improves crystallization of measles virus hemagglutinin.2008

    • Author(s)
      Hashiguchi, et al.
    • Journal Title

      Journal of Virological Methods 149

      Pages: 171-174

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient Multiplication of Human Metapneumovirus in Vero Cells Expressing the Transmembrane Serine Protease TMPRSS2.2008

    • Author(s)
      Shirogane, et al.
    • Journal Title

      Journal of Virology 82

      Pages: 8942-8946

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measles virus circumvents the host interferon response by different actions of the C and V proteins.2008

    • Author(s)
      Nakatsu, et al.
    • Journal Title

      Journal of Virology 82

      Pages: 8296-8306

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measles virus possessing the polymerase protein genes of the Edmonston vaccine strain exhibit attenuated gene expression and growth in cultured cells and SLAM-knockin mice.2008

    • Author(s)
      Takeda, et al.
    • Journal Title

      Journal of Virology 82

      Pages: 11979-11984

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus

    • Author(s)
      Shirogane, et al.
    • Journal Title

      THE JOURNAL OF BIOLOGICAL CHEMISTRY (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Measles virus infects epithelial cells.2010

    • Author(s)
      Takeda M, Shirogane Y, Tahara M, Hashiguchi T, Ikegame S, Iwasaki M, Nakamura T, Maenaka K, Yanagi Y
    • Organizer
      Negative Strand Virus Meeting 2010.
    • Place of Presentation
      Brugge, Belgium
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular basis for efficient transmission of measles virus.2010

    • Author(s)
      竹田誠
    • Organizer
      International Symposium on Organella Network : Microbiology, Immunology, and Cell Biology.
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスの上皮細胞感染機構2010

    • Author(s)
      竹田誠、白銀勇太、田原舞乃、中津祐一郎、橋口隆生、柳雄介
    • Organizer
      第58回日本ウイルス学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスHタンパク質アミノ酸546番目のグリシン変異における上皮細胞への感染性および機能変化2010

    • Author(s)
      關文緒、染谷健二、田原舞乃、中津祐一郎、駒瀬勝啓、竹田誠
    • Organizer
      第58回日本ウイルス学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] イメージング技術を用いた麻疹ウイルスLタンパク質の細胞内動態の解析2010

    • Author(s)
      中津祐一郎、鈴木忠樹、馬学旻、關文緒、駒瀬勝啓、柳雄介、竹田誠
    • Organizer
      第58回日本ウイルス学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] Measles virus infects epithelial cells.2010

    • Author(s)
      Takeda, et al.
    • Organizer
      Negative Strand Virus Meeting 2010
    • Place of Presentation
      Brugge, Belgium
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular basis for efficient transmission of measles virus.2010

    • Author(s)
      Takeda
    • Organizer
      International Symposium on Organella Network
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2010 Annual Research Report
  • [Presentation] 麻疹ウイルスの上皮細胞感染機構2010

    • Author(s)
      竹田誠, ら
    • Organizer
      日本ウイルス学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Annual Research Report
  • [Presentation] Antigenic variations among currently circulating wild type measles virus strains.2010

    • Author(s)
      Tahara, et al.
    • Organizer
      Negative Strand Virus Meeting 2010
    • Place of Presentation
      Brugge, Belgium
    • Related Report
      2010 Annual Research Report
  • [Presentation] 麻疹ウイルス主要表面抗原Hタンパク質の抗原性変化2010

    • Author(s)
      田原舞乃, ら
    • Organizer
      日本ウイルス学会
    • Place of Presentation
      徳島
    • Related Report
      2010 Annual Research Report
  • [Presentation] 麻疹ウイルス:病原性発現の分子基盤2009

    • Author(s)
      竹田誠、柳雄介
    • Organizer
      第57回日本ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 上皮間葉転換の誘導によって極性上皮細胞の麻疹ウイルスに対する感受性がなくなる2009

    • Author(s)
      白銀勇太、竹田誠、橋口隆生、田原舞乃、中村崇規、柳雄介
    • Organizer
      第57回日本ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスHタンパク質と受容体SLAMの複合体の結晶構造と麻疹ウイルスの細胞侵入機構2009

    • Author(s)
      橋口隆生、尾瀬農之、上敷領淳、竹田誠、前仲勝実、柳雄介
    • Organizer
      第57回日本ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ワクシニアウイルスフリーの高効率麻疹ウイルス回収系2009

    • Author(s)
      竹田誠、岡村晃資、白銀勇太、池亀聡、柳雄介
    • Organizer
      第57回日本ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスCタンパク質の役割2009

    • Author(s)
      竹田, ら
    • Organizer
      第74回 日本インターフェロン・サイトカイン学会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] 麻疹ウイルス:病原性発現の分子基盤2009

    • Author(s)
      竹田, ら
    • Organizer
      第57回 日本ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] Measles virus has an intrinsic ability to infect both immune and polarized epithelial cells via two distinctive mechanisms.2008

    • Author(s)
      Takeda M, Hashiguchi T, Tahara M, Yanagi Y
    • Organizer
      The 8th Awaji International Forum on Infection and Immunity.
    • Place of Presentation
      Awaji Island, Hyogo, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Human metapneumovirus grows efficiently in Vero cells expressing transmembrane serine protease TMPRSS2.2008

    • Author(s)
      Shirogane Y, Takeda M, Iwasaki M, Ishiguro, N, Takeuchi H, Nakatsu Y, Tahara M, Kikuta H, Yanagi Y
    • Organizer
      The 8th Awaji International Forum on Infection and Immunity.
    • Place of Presentation
      Awaji Island, Hyogo, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Crystal structure of the measles virus hemagglutinin sheds light on its interaction with cellular receptors and antibodies.2008

    • Author(s)
      Hashiguchi T, Takeda M, Maenaka K, Yanagi Y
    • Organizer
      27th Annual Meeting of American Society for Virology.
    • Place of Presentation
      Ithaca, New York
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスの極性上皮細胞からの出芽機構2008

    • Author(s)
      竹田誠、岩崎正治、池亀聡、田原舞乃、柳雄介
    • Organizer
      第45回日本ウイルス学会九州支部総会
    • Place of Presentation
      熊本
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスの極性細胞侵入および出芽機構2008

    • Author(s)
      竹田誠、橋口隆生、田原舞乃、岩崎正治、池亀聡、柳雄介
    • Organizer
      第56回日本ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report
  • [Presentation] 膜貫通型セリンプロテアーゼTMPRSS2はヒトメタニューモウイルスの多段階増殖を促進する2008

    • Author(s)
      白銀勇太、竹田誠、岩崎正治、石黒信久、竹内宏樹、中津祐一郎、田原舞乃、菊田英明、柳雄介
    • Organizer
      第56回日本ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスHタンパク質による受容体認識の構造基盤2008

    • Author(s)
      橋口隆生、竹田誠、田原舞乃、池亀聡、大野真治、柳雄介
    • Organizer
      第56回日本ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report
  • [Presentation] 麻疹ウイルスの極性細胞侵入および出芽機構2008

    • Author(s)
      竹田ら
    • Organizer
      第56回 日本ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2008 Annual Research Report
  • [Presentation] 麻疹ウイルスの極性上皮細胞からの出芽機構2008

    • Author(s)
      竹田ら
    • Organizer
      第45回 日本ウイルス学会九州支部総会
    • Place of Presentation
      熊本
    • Related Report
      2008 Annual Research Report
  • [Presentation] Measles virus has an intrinsic ability to infect both immune and polarized epithelial cells via two distinctive mechanisms.2008

    • Author(s)
      Takeda, et al.
    • Organizer
      The 8th Awaii International Forum on Infection and Immunity.
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Book] 分子予防環境医学生命科学研究の予防・環境医学への統合(分子予防環境医学研究会(編)改訂版)(麻疹ウイルス)2010

    • Author(s)
      關文緒、竹田誠
    • Publisher
      本の泉社
    • Related Report
      2010 Final Research Report
  • [Book] 分子予肺環境医学(分子予防環境医学研究会(編))改訂版2010

    • Author(s)
      關文緒、竹田誠(分担執筆)
    • Total Pages
      8
    • Publisher
      本の泉社
    • Related Report
      2010 Annual Research Report
  • [Book] Current Topics in Microbiology and Immunology(Griffin, D.E. and Oldstone, M.B.A. ed.)(Measles virus receptors. 329)2009

    • Author(s)
      Yanagi Y, Takeda M, Ohno S, Hashiguchi T
    • Publisher
      Measles history and basic biology.
    • Related Report
      2010 Final Research Report
  • [Book] 医科ウイルス学(改訂3版)(高田賢蔵(編))(パラミクソウイルス科)2009

    • Author(s)
      竹田誠、柳雄介
    • Publisher
      南江堂
    • Related Report
      2010 Final Research Report
  • [Book] 実験医学(光山正雄、北潔、野本明男(編))(麻疹ウイルスの受容体とトロピズム 感染症-ウイルス・細菌・寄生虫の感染戦略 27)2009

    • Author(s)
      竹田誠、柳雄介
    • Publisher
      羊土社
    • Related Report
      2010 Final Research Report
  • [Book] 蛋白質核酸酵素(木下タロウ、熊之郷淳、竹田潔、松浦善治、川端重忠(編))(感染現象麻疹ウイルスの増殖戦略 感染現象その理解の深化から疾患制御への展望 54)2009

    • Author(s)
      竹田誠、柳雄介
    • Publisher
      共同出版
    • Related Report
      2010 Final Research Report
  • [Book] Current Topics in Microbiology and Immunology 3292009

    • Author(s)
      Yanagi, et al.
    • Total Pages
      195
    • Publisher
      Measles history and basic biology
    • Related Report
      2009 Annual Research Report
  • [Book] 医科ウイルス学 改訂第3版 高田賢蔵編集2009

    • Author(s)
      竹田, ら
    • Total Pages
      485
    • Publisher
      南江堂
    • Related Report
      2009 Annual Research Report
  • [Book] 医科ウイルス学 改訂第3版 高田賢蔵編集2009

    • Author(s)
      竹田ら
    • Total Pages
      485
    • Publisher
      南江堂
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.nih.go.jp/niid/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/virus/index.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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