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Studies on viral factors that contribute to severe infection of enterovirus 71

Research Project

Project/Area Number 18H02667
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KOIKE Satoshi  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 分野長 (30195630)

Co-Investigator(Kenkyū-buntansha) 市村 宏  金沢大学, 医学系, 教授 (10264756)
小林 郷介  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 主席研究員 (80644989)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsエンテロウイルス71 / 病原性 / 神経病原性 / 点突然変異 / 騒動組換え / 相同組換え
Outline of Final Research Achievements

EV71, a causative agent of hand, foot and mouth disease, sometimes causes central nervous system complications. The reason for this is that it undergoes a virulent mutation during transmission. We analyzed the pathogenicity of the viruses using clinical isolates and EV71-susceptible Scavenger receptor B2 transgenic mice. The viruses showed different degrees of virulence in different epidemics, suggesting the fluctuation of the virulence by introduced mutations. We generated recombinant viruses of both virulent and avirulent strains and found that mutations in the 5'-UTR played an important role in determining the virulence.

Academic Significance and Societal Importance of the Research Achievements

ウイルスは生態系の中で塩基置換や相同組換えを繰り返し、重篤な感染症の原因ウイルスとして変化(進化)していくと考えられ、EV71もそのモデルの一つと考えられる。その過程の解明はウイルス学の概念上重要で一般化して考える意義が十分にある。さらに、その解明は新興・再興感染症出現のメカニズムを解明することにつながり、社会にいち早く注意喚起情報を発出することができ、社会的な貢献も大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (17 results)

All 2020 2019 2018 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (5 results)

  • [Journal Article] エンテロウイルス71の病原性に関する基礎研究2020

    • Author(s)
      小池 智
    • Journal Title

      臨床とウイルス

      Volume: 48 Pages: 330-335

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Newly emerged enterovirus-A71 C4 sublineage may be more virulent than B5 in the 2015?2016 hand-foot-and-mouth disease outbreak in northern Vietnam2020

    • Author(s)
      Chu Son T.、Kobayashi Kyousuke、Bi Xiuqiong、Ishizaki Azumi、Tran Tu T.、Phung Thuy T. B.、Pham Chung T. T.、Nguyen Lam V.、Ta Tuan A.、Khu Dung T. K.、Agoh Masanobu、Pham An N.、Koike Satoshi、Ichimura Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 159-159

    • DOI

      10.1038/s41598-019-56703-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heparan sulfate attachment receptor is a major selection factor for attenuated enterovirus 71 mutants during cell culture adaptation2020

    • Author(s)
      Kobayashi Kyousuke、Mizuta Katsumi、Koike Satoshi
    • Journal Title

      PLOS Pathogens

      Volume: 16 Issue: 3 Pages: e1008428-e1008428

    • DOI

      10.1371/journal.ppat.1008428

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular receptors for enterovirus A712020

    • Author(s)
      Kobayashi Kyousuke、Koike Satoshi
    • Journal Title

      Journal of Biomedical Science

      Volume: 27 Issue: 1 Pages: 23-23

    • DOI

      10.1186/s12929-020-0615-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amino Acid Variation at VP1-145 of Enterovirus 71 Determines Attachment Receptor Usage and Neurovirulence in Human Scavenger Receptor B2 Transgenic Mice2018

    • Author(s)
      Kyousuke Kobayashi, Yui Sudaka, Ayako Takashino, Ayumi Imura, Ken Fujii, Satoshi Koike
    • Journal Title

      Journal of Virology

      Volume: 92 Issue: 15

    • DOI

      10.1128/jvi.00681-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VP1 Amino Acid Residue 145 of Enterovirus 71 Is a Key Residue for Its Receptor Attachment and Resistance to Neutralizing Antibody during Cynomolgus Monkey Infection2018

    • Author(s)
      Fujii Ken、Sudaka Yui、Takashino Ayako、Kobayashi Kyousuke、Kataoka Chikako、Suzuki Tadaki、Iwata-Yoshikawa Naoko、Kotani Osamu、Ami Yasushi、Shimizu Hiroyuki、Nagata Noriyo、Mizuta Katsumi、Matsuzaki Yoko、Koike Satoshi
    • Journal Title

      Journal of Virology

      Volume: 92 Issue: 15 Pages: 1-17

    • DOI

      10.1128/jvi.00682-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] エンテロウイルス71の病原性に関する基礎研究2020

    • Author(s)
      小池智
    • Organizer
      第61回日本臨床ウイルス学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] An inactivated EV71 vaccine candidate provides cross-protection against heterogous subgenotypes in human SCARB2 transgenic mice2020

    • Author(s)
      Subash CD, Larwal L, Springer Z, Vang, Tamura K, Takashino A, Kobayashi K, Koike S, Adachi S, Fukuda S, Thomson , Rao R, Dean H
    • Organizer
      American Society for Virology 39th Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Virulence analysis of enterovirus 71 isolated from Hand-foot-mouth disease patients in Japan and Vietnam for identification of virulence determinant2019

    • Author(s)
      Kobayashi K, Chu ST, Mizuta K, Nishimura H, Ichimura H, Koike S
    • Organizer
      the 67th annual meeting of the Japansese society for virology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Use of attachment receptor, heparan sulfate proteoglycan, negatively affects neurovirulence of VP1-145 variants of enterovirus 712018

    • Author(s)
      Kobayashi K, Sudaka Y, Takashino A, Imura A, Fujii K, Koike S
    • Organizer
      The 20 th Meeting of the European Study Group on the Molecular Biology of Picornaviruses
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tissue culture adaptation of enterovirus 71 selects mutant viruses that bind to HS and are attenuated in vivo2018

    • Author(s)
      Kobayashi K, Son Thanh Chu, Takashino A, Aoki Y, Matoba Y, Mizuta K, Nishimura H, Ichimura H, Koike S
    • Organizer
      The 66th Annual Meeting of The Japanese Society for Virology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Epidemiological and Virological Characterization of the Enterovirus Causing Hand Foot and Mouth Disease in Northern Vietnam, 2015-20112018

    • Author(s)
      Son Thanh Chu, Bi X, Ishizaki A, Masanobu Ago M, yousuke Kobayashi K, Koike, S Ichimura H
    • Organizer
      The 66th Annual Meeting of The Japanese Society for Virology
    • Related Report
      2018 Annual Research Report
  • [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

      https://www.igakuken.or.jp/neurovirology/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 未来を話そう!プロジェクト研究の紹介 ウイルス感染プロジェクト(一般向け)

    • URL

      https://www.igakuken.or.jp/project/to-tomin/to-pro04.html

    • Related Report
      2020 Annual Research Report
  • [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/project/detail/neurovirology.html

    • Related Report
      2019 Annual Research Report
  • [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(一般向け)

    • URL

      http://www.igakuken.or.jp/project/to-tomin/to-pro04.html

    • Related Report
      2019 Annual Research Report
  • [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/

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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