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Study on pathogenesis of flaccid paralysis caused by enterovirus D68 using animal models

Research Project

Project/Area Number 19H03626
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Nagata Noriyo  国立感染症研究所, 感染病理部, 室長 (30270648)

Co-Investigator(Kenkyū-buntansha) 西村 順裕  国立感染症研究所, ウイルス第二部, 主任研究官 (00392316)
清水 博之  国立感染症研究所, ウイルス第二部, 主任研究官 (90270644)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsエンテロウイルスD68 / 動物モデル / 弛緩性麻痺 / 神経病原性 / 急性弛緩性麻痺 / エンテロウイルス / 麻痺
Outline of Research at the Start

エンテロウイルスD68は呼吸器感染症を起こすことが知られていたが、2014年に北米で発生したエンテロウイルスD68による急性重症呼吸器感染症のアウトブレイクと同時期にポリオ様の麻痺を発症した患児が多数報告された。国内でも2015年のエンテロウイルスD68流行時に麻痺患者の咽頭拭い液等からこのウイルスが検出されたことから、神経病変とウイルス感染の関連性が疑われているが、現在まで直接的証明には至っていない。本研究ではエンテロウイルスD68の神経病原性の解明を最終目標として感染動物モデルを確立し、このウイルスの急性重症呼吸器感染症と神経病原性に関与するウイルス側因子と宿主側因子を明らかにする。

Outline of Final Research Achievements

The neuropathogenicity of EV-D68 in mice and cynomolgus monkeys was examined using a strain of H1HeLa cell-passaged EV-D68. Intracerebral inoculation into neonatal mice, intraspinal inoculation into adult mice, and intraspinal inoculation into monkeys with EV-D68 resulted flaccid paralysis in these animals. Histopathological examination revealed that these paralyses were due to loss of neurons in the anterior horn of the spinal cord after virus infection.

Academic Significance and Societal Importance of the Research Achievements

EV-D68感染症と弛緩性麻痺の関連性が強く疑われているが、詳細は不明である。本研究では実験動物を用いてEV-D68の神経病原性に関する病態病理解析とモデルの確立を行った。これらの動物モデルはEV-D68感染症のための新規治療法、予防法の確立のみならず、その発症機序の理解に貢献すると期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Open Access: 4 results,  Peer Reviewed: 7 results) Presentation (3 results) (of which Invited: 2 results)

  • [Journal Article] エンテロウイルスによる多様な神経感染症: 動物モデルから得られた知見2022

    • Author(s)
      永田 典代
    • Journal Title

      NEUROINFECTION

      Volume: 27 Issue: 1 Pages: 90

    • DOI

      10.34397/jsnd.27.1_90

    • ISSN
      1348-2718, 2435-2225
    • Related Report
      2022 Annual Research Report
    • Open Access
  • [Journal Article] Macrophage depletion reactivates fecal virus shedding following resolution of acute hepatitis A in Ifnar1-/- mice.2022

    • Author(s)
      Shiota T, Matsuda M, Zheng X, Nagata N, Ishii K, Suzuki R, Muramatsu M, Takimoto K, Hanaki K, Lemon SM, McGivern D, Hirai-Yuki A
    • Journal Title

      Journal of Virology

      Volume: 96 Issue: 23 Pages: 1-14

    • DOI

      10.1128/jvi.01496-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection2022

    • Author(s)
      Iwata-Yoshikawa Naoko、Shiwa Nozomi、Sekizuka Tsuyoshi、Sano Kaori、Ainai Akira、Hemmi Takuya、Kataoka Michiyo、Kuroda Makoto、Hasegawa Hideki、Suzuki Tadaki、Nagata Noriyo
    • Journal Title

      Science Advances

      Volume: 8 Issue: 1 Pages: 1-17

    • DOI

      10.1126/sciadv.abh3827

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coxsackieviruses A6 and A16 associated with hand, foot, and mouth disease in Vietnam, 2008?2017: Essential information for rational vaccine design2020

    • Author(s)
      Hoa-Tran Thi Nguyen、Dao Anh Thi Hai、Nguyen Anh The、Kataoka Chikako、Takemura Taichiro、Pham Chau Ha、Vu Hung Manh、Hong Ta Thi Thu、Ha Nguyen Thi Viet、Duong Tran Nhu、Thanh Nguyen Thi Hien、Shimizu Hiroyuki
    • Journal Title

      Vaccine

      Volume: 38 Issue: 52 Pages: 8273-8285

    • DOI

      10.1016/j.vaccine.2020.11.031

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] エンテロウイルス感染による急性弛緩性麻痺の病理2020

    • Author(s)
      永田典代、長谷川秀樹、清水博之、斎藤博之
    • Journal Title

      病原微生物検出情報

      Volume: 41 Pages: 25-27

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Development of an Enterovirus 71 Vaccine Efficacy Test Using Human Scavenger Receptor B2 Transgenic Mice2020

    • Author(s)
      Imura Ayumi、Sudaka Yui、Takashino Ayako、Tamura Kanami、Kobayashi Kyousuke、Nagata Noriyo、Nishimura Hidekazu、Mizuta Katsumi、Koike Satoshi
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 6 Pages: 1-14

    • DOI

      10.1128/jvi.01921-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuropathology in Neonatal Mice After Experimental Coxsackievirus B2 Infection Using a Prototype Strain, Ohio-12019

    • Author(s)
      Ushioda Waka、Kotani Osamu、Kawachi Kengo、Iwata-Yoshikawa Naoko、Suzuki Tadaki、Hasegawa Hideki、Shimizu Hiroyuki、Takahashi Kimimasa、Nagata Noriyo
    • Journal Title

      Journal of Neuropathology & Experimental Neurology

      Volume: 79 Issue: 2 Pages: 209-225

    • DOI

      10.1093/jnen/nlz124

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enterovirus D68 respiratory infection in a children's hospital in Japan in 20152019

    • Author(s)
      Funakoshi Yu、Ito Kenta、Morino Saeko、Kinoshita Kazue、Morikawa Yoshihiko、Kono Tatsuo、Doan Yen Hai、Shimizu Hiroyuki、Hanaoka Nozomu、Konagaya Masami、Fujimoto Tsuguto、Suzuki Ai、Chiba Takashi、Akiba Tetsuya、Tomaru Yasuhiro、Watanabe Ken、Shimizu Norio、Horikoshi Yuho
    • Journal Title

      Pediatrics International

      Volume: 61 Issue: 8 Pages: 768-776

    • DOI

      10.1111/ped.13903

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial MRI findings of acute flaccid myelitis during an outbreak of enterovirus D68 infection in Japan2019

    • Author(s)
      Okumura Akihisa、Mori Harushi、Fee Chong Pin、Kira Ryutaro、Torisu Hiroyuki、Yasumoto Sawa、Shimizu Hiroyuki、Fujimoto Tsuguto、Tanaka-Taya Keiko
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 5 Pages: 443-451

    • DOI

      10.1016/j.braindev.2018.12.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] エンテロウイルスによる多様な神経感染症: 動物モデルから得られた知見2021

    • Author(s)
      永田典代
    • Organizer
      第25回日本神経感染症学会総会・学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 急性弛緩性脊髄炎とエンテロウイルス:動物モデルから得られた知見2020

    • Author(s)
      永田 典代
    • Organizer
      日本神経免疫学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウスモデルにおけるエンテロウイルスD68の神経病原性2019

    • Author(s)
      永田 典代、宮崎 誠、斎藤 博之、柴田 ちひろ、ドゥアン イェンハイ、荒尾 雄二郎、岩田(吉河) 奈織子、清水 博之、長谷川 秀樹
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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