Study on roles of human metapneumovirus accessory proteins in viral pathogenecity

• Project/Area Number: 22590414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: GOTOH Bin 滋賀医科大学, 医学部, 教授 (00211920)
• Co-Investigator(Renkei-kenkyūsha): KITAGAWA Yoshinori 滋賀医科大学, 医学部, 助教 (00444448)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヒトメタニューモウイルス / アクセサリータンパク質 / 転写複製 / M2-2タンパク質 / インターフェロン / TLR7/9 / IRF7 / 形質細胞様樹状細胞 / アクセサリー蛋白質 / M2-2蛋白質 / TRAF6

Research Abstract

The present study has uncovered the following functions of human metapneumovirus accessory protein M2-2. Firstly, M2-2 binds to viral RNA polymerase L and negatively regulates replication and transcription of viral genome. Secondly, M2-2 potentially serves as an interferon (IFN) antagonist that inhibits alpha IFN production. This activity is independent of the inhibitory activity against genome replication and transcription, and ascribed to the blockade of Toll-like receptor 7/9-dependent signaling in plasmacytoid dendritic cells characteristic of producing a large amount of alpha IFN.

Research Products

• [Journal Article] Masae Itoh. F-actin modulates measles virus cell-cell fusion and assembly by altering the interaction between the matrix protein and the cytoplasmic tail of hemagglutinin (2013)
  • Author(s): Hiroshi Wakimoto, Masakatsu Shimodo, Yuto Satoh, Yoshinori Kitagawa, Kaoru Takeuchi, Bin Gotoh
  • Journal Title: Journal of Virology Volume: 87 Issue: 4 Pages: 1974-1984
  • DOI: 10.1128/jvi.02371-12
  • Peer Reviewed
• [Journal Article] Expeditious neutralization assay for human metapneumovirus based on a recombinant virus expressing Renilla luciferase (2013)
  • Author(s): Min Zhou, Yoshinori Kitagawa, Mayu Yamaguchi, Chika Uchiyama, Masae Itoh, Bin Gotoh.
  • Journal Title: Journal of Clinical Virology Volume: 56 Issue: 1 Pages: 31-36
  • DOI: 10.1016/j.jcv.2012.09.014
  • Peer Reviewed
• [Journal Article] A Tryptophan-rich Motif in the Human Parainfluenza Virus Type 2 V Protein is Critical for the Blockade of Toll-Like Receptor 7/9 Dependent Signaling (2011)
  • Author(s): Yoshinori Kitagawa, Mayu Yamaguchi, Min Zhou, Takayuki Komatsu, Machiko Nishio, Tsuyoshi Sugiyama, Kenji Takeuchi, Masae Itoh, Bin Gotoh
  • Journal Title: Journal of Virology Volume: 85 Issue: 9 Pages: 4606-4611
  • DOI: 10.1128/jvi.02012-10
  • Peer Reviewed
• [Journal Article] A Tryptophan-rich Motif in the Human Parainfluenza Virus Type 2 V Protein is Critical for the Blockade of Toll-Like Receptor 7/9 Dependent Signaling. (2011)
  • Author(s): Yoshinori Kitagawa
  • Journal Title: Journal of Virology Volume: 85(in press)
  • Peer Reviewed
• [Journal Article] Human metapneumovirus M2-2 protein inhibits viral transcription and replication (2010)
  • Author(s): Yoshinori Kitagawa, Min Zhou, Mayu Yamaguchi, Takayuki Komatsu, Kenji Takeuchi, Masae Itoh, Bin Gotoh
  • Journal Title: Microbes and Infection Volume: 12 Issue: 2 Pages: 135-145
  • DOI: 10.1016/j.micinf.2009.11.002
  • Peer Reviewed
• [Presentation] 麻疹ウイルス感染様式の温度依存性 (2012)
  • Author(s): 脇本浩史、閻東怡、藤友人、竹内薫、北川善紀、後藤 敏、伊藤正恵
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-15
• [Presentation] パラミクソウイルス C タンパク質と IRF7 依存性インターフェロン産生シグナル (2012)
  • Author(s): 山口まゆ、北川善紀、周 敏、小松孝行、竹内健司、伊藤正恵、後藤 敏
  • Organizer: パラミクソウイルス Cタンパク質と IRF7 依存性インターフェロン産生シグナル
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-15
• [Presentation] TLR7/9 依存性インターフェロン産生抑制における V タンパク質と TRAF6 の相互作用の重要性 (2012)
  • Author(s): 北川善紀、山口まゆ、小松孝行、周 敏、竹内健司、西尾真智子、伊藤正恵、後藤 敏
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-14
• [Presentation] ヒトメタニューモウイルス中和抗体価迅速測定法の開発 (2012)
  • Author(s): 周 敏、北川善紀、内山知佳、山口まゆ、伊藤正恵、後藤 敏 伊藤正恵、後藤 敏
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] TLR7/9依存性インターフェロン産生抑制におけるVタンパク質とTRAF6の相互作用の重要性 (2012)
  • Author(s): 北川善紀
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] パラミクソウイルスCタンパク質とIRF7依存性インターフェロン産生シグナル (2012)
  • Author(s): 山口まゆ
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Antagonistic activity of paramyxovirus V proteins against Toll-like receptor 7/9 dependent alpha interferon induction (2011)
  • Author(s): Yoshinori Kitagawa, Mayu Yamaguchi, Min Zhou, Takayuki Komatsu, Machiko Nishio, Tsuyoshi Sugiyama, Kenji Takeuchi, Masae Itoh, Bin Gotoh
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-13
• [Presentation] Masae Itoh. F-actin suppresses measles virus infectious particle formation by interfering with the interaction between the Matrix (M) and the hemagglutinin (H) proteins (2011)
  • Author(s): Hiroshi Wakimoto, Masakatsu Shimodoh, Yoshinori Kitagawa, Kaoru Takeuchi, Bin Gotoh
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-13
• [Presentation] F-actin suppresses measles virus infectious particle formation by interfe ring with the interaction between the Matrix (M) and the hemagglutinin (H) proteins (2011)
  • Author(s): Hiroshi Wakimoto
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-13
• [Presentation] 宿主インターフェロンシステムとパラミクソウイルスアクセサリー蛋白質 (2010)
  • Author(s): 後藤 敏
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] パラミクソウイルス V 蛋白質はTRAF6 による IRF7 のユビキチン化を阻害する (2010)
  • Author(s): 北川善紀、山口まゆ、周 敏、小松孝行、竹内健司、西尾真智子、伊藤正恵、後藤 敏
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] センダイウイルス C 蛋白質による TLR7/9 シグナル伝達の阻害 (2010)
  • Author(s): 山口まゆ、北川善紀、周 敏、小松孝行、竹内健司、伊藤正恵、後藤 敏
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] 宿主インターフェロンシステムとパラミクソウイルスアクセサリー蛋白質 (2010)
  • Author(s): 後藤敏
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: あわぎんホール(徳島県)(招待講演)
  • Year and Date: 2010-11-08
• [Presentation] パラミクソウイルスV蛋白質はTRAF6によるIRF7のユビキチン化を阻害する (2010)
  • Author(s): 北川善紀
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: あわぎんホール(徳島県)
  • Year and Date: 2010-11-08
• [Presentation] センダイウイルスC蛋白質によるTLR7/9シグナル伝達の阻害 (2010)
  • Author(s): 山口まゆ
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: あわぎんホール(徳島県)
  • Year and Date: 2010-11-08
• [Book] Evolution from Mouse Pathogen to a State-of-the-art Tool in Virus Research and Biotechnology in "The Biology of Paramyxoviruses" (2011)
  • Author(s): Yoshiyuki Nagai, Akira Takakura, Takashi Irie, Yoshikazu Yonemitsu, Bin Gotoh
  • Publisher: Caister Academic Press
• [Book] The Biology of Paramyxoviruses (ed.) Siba K, Samal (2011)
  • Author(s): Yoshiyuki Nagai
  • Publisher: Caister Academic Press, Norwich U.K.
• [Book] The Biology of Paramyxoviruses (ed.) Siba K.Samal (2011)
  • Author(s): Yoshiyuki Nagai
  • Publisher: Caister Academic Press, Norwich U.K.
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/db/pub_top.php