Role of inhibitory activity of paramyxoviruses against host alpha-interferon production in virus pathogenicity

• Project/Area Number: 23790499
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: KITAGAWA Yoshinori 滋賀医科大学, 医学部, 助教 (00444448)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: パラミクソウイルス / IFNアンタゴニスト / アクセサリー蛋白質 / 自然免疫 / インターフェロン / TLR-7/9経路

Research Abstract

Paramyxovirus V proteins block Toll-like receptor 7 (TLR7)- and TLR9-dependent signaling leading to alpha interferon production. However, the detailed mechanisms remain unclear. Here we revealed that the human parainfluenza virus type 2 (HPIV2) V protein interacted with TRAF6 and inhibited not only TRAF6-mediated lysine 63 (K63)-linked polyubiquitination but also subsequent phosphorylation of IRF7. These results suggest that the HPIV2 V protein prevents TRL7/9-dependent interferon induction by inhibiting TRAF6-mediated K63-linked polyubiquitination of IRF7.

Research Products

• [Journal Article] An anti-interferon activity shared by paramyxovirus C proteins : Inhibition of Toll-like receptor 7/9-dependent alpha interferon induction (2014)
  • Author(s): Yamaguchi M, Kitagawa Y, Zhou M, Itoh M, Gotoh B
  • Journal Title: FEBS Letters Volume: 588 Pages: 28-34
  • Peer Reviewed
• [Journal Article] An anti-interferon activity shared by paramyxovirus C proteins: Inhibition of Toll-like receptor 7/9-dependent alpha interferon induction. (2014)
  • Author(s): Mayu Yamaguchi, Yoshinori Kitagawa, Min Zhou, Masae Itoh, and Bin Gotoh
  • Journal Title: FEBS letters Volume: 588 Issue: 1 Pages: 28-34
  • DOI: 10.1016/j.febslet.2013.11.015
  • Peer Reviewed
• [Journal Article] Human Parainfluenza Virus Type 2 V Protein Inhibits TRAF6-mediated Ubiquitination of IRF7 to Prevent Toll-like Receptor 7 (TLR7)- and TLR9-Dependent Interferon Induction (2013)
  • Author(s): Kitagawa Y, Yamaguchi M, Zhou M, Nishio M, Itoh M, Gotoh B
  • Journal Title: J. Virol Volume: 87 Pages: 7966-7976
  • Peer Reviewed
• [Journal Article] Human Parainfluenza Virus Type 2 V Protein Inhibits TRAF6-Mediated Ubiquitination of IRF7 To Prevent TLR7- and TLR9-Dependent Interferon Induction. (2013)
  • Author(s): Kitagawa Y, Yamaguchi M, Zhou M, Nishio M, Itoh M, Gotoh B.
  • Journal Title: J. Virol. Volume: 87 Issue: 14 Pages: 7966-7976
  • DOI: 10.1128/jvi.03525-12
  • 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] 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] A tryptophan-rich motif in the human parainfluenza virus type 2 V protein is critical for the blockade of toll-like receptor 7 (TLR7)- and TLR9-dependent signaling (2011)
  • Author(s): Kitagawa Y, Yamaguchi M, Zhou M, Komatsu T, Nishio M, Sugiyama T, Takeuchi K, Itoh M, Gotoh B
  • Journal Title: J. Virol Volume: 85 Pages: 4606-4611
  • 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
• [Presentation] 形質細胞様樹状細胞のIFN-α産生とヒトメタニューモウイルス (2013)
  • Author(s): 北川善紀、山口まゆ、周敏、伊藤正恵、後藤敏
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-11
• [Presentation] 形質細胞様樹状細胞のIFN-α産生とヒトメタニューモウイルス (2013)
  • Author(s): 北川善紀、山口まゆ、周敏、伊藤正恵、後藤敏
  • Organizer: 日本ウイルス学会学術総会
  • Place of Presentation: 神戸市
• [Presentation] ヒトメタニューモウイルスのpH依存性細胞融合とウイルス侵入様式 (2013)
  • Author(s): 周敏、北川善紀、山口まゆ、伊藤正恵、後藤敏
  • Organizer: 日本ウイルス学会学術総会
  • Place of Presentation: 神戸市
• [Presentation] 麻疹ウイルスF蛋白のプロテアーゼ感受性決定要因 (2013)
  • Author(s): 佐藤友人、正垣博子、廣瀬充宏、脇本浩史、高橋健一、北川善紀、竹内薫、後藤敏、伊藤正恵
  • Organizer: 日本ウイルス学会学術総会
  • Place of Presentation: 神戸市
• [Presentation] TLR7/ 9依存性インターフェロン産生抑制におけるV蛋白質とTRAF6と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: 日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-14
• [Presentation] TLR7/9依存性インターフェロン産生抑制におけるV蛋白質とTRAF6と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: 日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [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、佐藤友人、竹内薫、北川善紀、後藤敏、伊藤正恵
  • Organizer: 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蛋白質と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: 日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [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
  • Organizer: 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): Kitagawa Y, Yamaguchi M, Zhou M, Komatsu T, Nishio M, Sugiyama T, Takeuchi K, Itoh M, Gotoh B
  • Organizer: International Union Microbiological Societies. 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-13
• [Presentation] Antagonistic activity of paramyxovirus V proteins against Toll-like receptor 7/9 dependent alpha interferon induction (2011)
  • Author(s): Kitagawa Y, Yamaguchi M, Zhou M, Komatsu T, Nishio M, Sugiyama T, Takeuchi K, Itoh M, Gotoh B
  • Organizer: International Union Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌市
• [Presentation] 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): Wakimoto H. Shimodoh M. Kitagawa Y. Takeuchi K. Gotoh B. Itoh M.
  • Organizer: International Union Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌市
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqmicro/
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/db/pub_top.php
• [Remarks] 滋賀医科大学 研究情報データベース 研究者総覧・研究業績一覧
  • URL: http://www.shiga-med.ac.jp/db/pub_top.php
• [Remarks] http://www.shiga-med.ac.jp/db/pub_top.php
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/db/pub_top.php