Identification of EV71 virulence diterminants using mouse model

• Project/Area Number: 15K08514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: FUJII Ken 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (10580201)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エンテロウイルス71 / 神経病原性 / EV71 / 動物モデル / ウイルス粒子 / VP1-145 / マウスモデル / 温度感受性 / エンテロウイルス

Outline of Final Research Achievements

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and sometimes causes severe or fatal neurological complications. The amino acid at VP1-145 determines virological characteristics of EV71. Viruses with glutamic acid (E) at VP1-145 (VP1-145E) are virulent in neonatal mice and transgenic mice expressing human scavenger receptor B2, whereas those with glutamine (Q) or glycine (G) are not. However, the contribution of this variation to pathogenesis in humans is not fully understood. We compared the virulence of VP1-145E and VP1-145G viruses of Isehara and C7/Osaka backgrounds in cynomolgus monkeys. VP1-145E, but not VP1-145G, viruses induced neurological symptoms. VP1-145E viruses were frequently detected in the tissues of infected monkeys. VP1-145G viruses were detected less frequently and disappeared quickly. Instead, mutants that had a G to E mutation at VP1-145 emerged, suggesting that VP1-145E viruses have a replication advantage in the monkeys.

Research Products

• [Presentation] The VP1 amino acid residue 145 of EV71 is a virulence determinant in a cynomolgus monkey model (2016)
  • Author(s): Ken Fujii, Yui Sudaka, Chikako Kataoka, Tadaki Suzuki, Naoko Iwata-Yoshikawa, Osamu Kotani, Yasushi Ami, Hiroyuki Shimizu, Noriyo Nagata and Satoshi Koike.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-10-23
• [Presentation] The VP1 amino acid residue 145 of EV71 is a virulence determinant in SCARB2-dependent infection. (2016)
  • Author(s): Ken Fujii, Yui Sudaka, Ayumi Imura, Ayako Takashino, Chikako Kataoka, Tadaki Suzuki, Naoko Iwata-Yoshikawa, Osamu Kotani, Yasushi Ami, Hiroyuki Shimizu, Noriyo Nagata and Satoshi Koike.
  • Organizer: The 19th Meeting of European Study Group on the Molecular Biology of Picornaviruses
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Remarks] 公益財団法人東京都医学総合研究所ウイルス感染プロジェクトホームページ
  • URL: http://www.igakuken.or.jp/neurovirology/
• [Remarks] 公益財団法人東京都医学総合研究所ウイルス感染プロジェクト
  • URL: http://www.igakuken.or.jp/neurovirology/index.html