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

2013 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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
• [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] 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] 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
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqmicro/
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/db/pub_top.php