The mechanism of infection of enterovirus71: through the receptor PSGL-1.

• Project/Area Number: 25860832
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KATAOKA Chikako 国立感染症研究所, その他部局等, 研究員 (10646623)
• Research Collaborator: SHIMIZU Hiroyuki ; NISHIMURA Yorihiro ; WAKITA Takaji ; AMI Yasushi ; NAGATA Noriyo ; SUZUKI Tadaki ; IWATA Naoko (YOSHIKAWA Naoko) ; KOTANI Osamu
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: エンテロウイルス / 感染動物モデル / 選択圧 / ウイルス学 / 病原性 / ウイルス感染 / 動物モデル / 神経ウイルス

Outline of Final Research Achievements

We identified PSGL-1 as an EV71 receptor before.In this study, we investigated viral replication, genetic stability, and the pathogenicity of PSGL-1-binding (PB with VP1-145G) and PSGL-1-nonbinding (non-PB with VP1-145E) strains of EV71 in a cynomolgus monkey model. Mild neurological symptoms, transient lymphocytopenia, and inflammatory cytokine responses were found predominantly in the non-PB-inoculated monkeys. After inoculation with EV71, almost all EV71 detected in clinical samples, central nervous system (CNS), and non-CNS tissues of both inoculated groups, possessed VP1-145E, suggesting a strong in vivo selection of VP1-145E variants and CNS spread presumably in a PSGL-1-independent manner. Thus, VP1-145E variants are mainly responsible for the development of viremia and neuropathogenesis in a non-human primate model, further suggesting the in vivo involvement of amino acid polymorphism at VP1-145 in cell-specific viral replication and pathogenesis in EV71-infected individuals.

Research Products

• [Journal Article] Alternative endocytosis pathway for productive entry of hepatitis C virus. (2014)
  • Author(s): Matsuda M, Suzuki R, Kataoka C, Watashi K, Aizaki H, Kato N, Matsuura Y, Suzuki T, Wakita T
  • Journal Title: J Gen Virol. Volume: 95(Pt 12) Issue: 12 Pages: 2658-67
  • DOI: 10.1099/vir.0.068528-0
  • Peer Reviewed / Open Access
• [Journal Article] Enterovirus 71 Binding to PSGL-1 on Leukocytes : VP1-145 Acts as a Molecular Switch to Control Receptor Interaction (2013)
  • Author(s): Nishimura Y, Lee H, Hafenstein S, Kataoka C, Wakita T, Bergelson JM, Shimizu H
  • Journal Title: PLoS Pathog Volume: 9 Issue: 7 Pages: e1003511-e1003511
  • DOI: 10.1371/journal.ppat.1003511
  • Peer Reviewed
• [Presentation] エンテロウイルス71のカニクイザルにおける病原性の免疫学的解析 (2014)
  • Author(s): 片岡周子、西村順裕、小谷治、鈴木忠樹、岩田奈織子、網康至、永田典代、清水博之
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜 会議センター
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] VP1-145 of enterovirus71 is one of the determinants for pathogenicity in a cynomolgus monkey model. (2014)
  • Author(s): Chikako Kataoka
  • Organizer: 18th International Picornavirus Meeting
  • Place of Presentation: Blankenberge, Belgium
• [Presentation] エンテロウイルス71のカニクイザルにおける病原性の解析 (2013)
  • Author(s): 片岡 周子
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場