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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390133
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kyushu University
• Principal Investigator: MAKOTO Takeda Kyushu University, ウイルス第三部, 部長 (40311401)
• Project Period (FY): 2008 – 2010

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
  • Year and Date: 20101100
• [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
  • Year and Date: 20101100
• [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
  • Year and Date: 20101100
• [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
  • Year and Date: 20100712-20100713
• [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
  • Year and Date: 20100621-20100625
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20081000
• [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
  • Year and Date: 20081000
• [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
  • Year and Date: 20081000
• [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
  • Year and Date: 20081000
• [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
  • Year and Date: 20080900
• [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
  • Year and Date: 20080900
• [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
  • Year and Date: 20080700
• [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
  • Total Pages: 210-217
  • Publisher: 本の泉社
• [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
  • Total Pages: 13-30
  • Publisher: Measles history and basic biology.
• [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
  • Total Pages: 342-352
  • Publisher: 南江堂
• [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
  • Total Pages: 128-134
  • Publisher: 羊土社
• [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
  • Total Pages: 908-912
  • Publisher: 共同出版
• [Remarks] ホームページ等