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Molecular basis of enterovirus 71 neuropathogenicity

Research Project

Project/Area Number 23390116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
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, ゲノム医科学研究分野, 副参事研究員 (30195630)

Co-Investigator(Kenkyū-buntansha) 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, 主任研究員 (10580201)
YAMAYOSHI Seiya  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, 研究員 (50529534)
Co-Investigator(Renkei-kenkyūsha) NAGATA Noriyo  国立感染症研究所, 感染病理部, 室長 (30270648)
SHIMIZU Hiroyuki  国立感染症研究所, ウイルス第二部, 室長 (90270644)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsエンテロウイルス71 / 神経病原性 / マウス感染モデル / 感染症 / ウイルス / ウイルス受容体 / 神経毒力 / 脳神経疾患
Outline of Final Research Achievements

The host range of enterovirus 71 (EV71) is restricted to primates with some exceptions. Therefore it was difficult to evalate the neurovirulence level of EV71 strains. We have established a transgenic mouse model that expressed a cellular receptor for EV71, human Scavenger receptor B2 (SCARB2). The transgenic mice became susceptible to EV71. They showed efficient EV71 replication in neurons in the CNS and neurological signs similar to those observed in human severe cases infected with EV71.
We inoculated several EV71 strains and compared the virulence of these strains. The inoculated virus exhibited different virulence levels, suggesting that the tg mice are useful model. We then evaluated the effect of a single amino acid substitution Gly to Glu at position 145 of the VP1 capsid protein. The virus with Glu at this position significantly increased the virulence compared to that with Gly. The result suggested that this amino acid is an important virulence determinant in EV71.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (16 results) (of which Invited: 5 results) Book (1 results) Remarks (5 results)

  • [Journal Article] Receptors for enterovirus 712014

    • Author(s)
      Yamayoshi S, Fujii K, Koike S
    • Journal Title

      Emerg. Microbes Infect

      Volume: 3 Issue: 1 Pages: 1-7

    • DOI

      10.1038/emi.2014.49

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections2014

    • Author(s)
      Kotani O, Iwata-Yoshikawa N, Suzuki T, Sato Y, Nakajima N, Koike S, Iwasaki T, Sata T, Yamashita T, Minagawa H, Taguchi F, Hasegawa H, Shimizu H, Nagata N
    • Journal Title

      Neuropathology

      Volume: 35 Issue: 2 Pages: 107-121

    • DOI

      10.1111/neup.12171

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic mous model for the study of enterovirus 71 pathogenesis2013

    • Author(s)
      Fujii K, Nagata N, SatoY, Ong KC, Wong KT, Yamayoshi S, Shimanuki M, Shitara H, Taya C, Koike S
    • Journal Title

      Proceedings of the National Academy of Science United States of America

      Volume: 110 Issue: 36 Pages: 14753-14758

    • DOI

      10.1073/pnas.1217563110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EMCV disrupts stress granules, the critical platform for triggering antiviral innate immune responses.2013

    • Author(s)
      Ng CS, Jogi M, Yoo JS, Onomoto K, Koike S, Iwasaki T, Yoneyama M, Kato H, Fujita T.
    • Journal Title

      J. Virol.

      Volume: 87 Issue: 17 Pages: 9511-9522

    • DOI

      10.1128/jvi.03248-12

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus712013

    • Author(s)
      Yamayoshi S, Ohka S, Fujii K, Koike S
    • Journal Title

      Journal of Virology

      Volume: 87 Pages: 3335-3347

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human SCARB2-dependent Infection by Coxsackievirus A7, A14, A16 and Enterovirus 712012

    • Author(s)
      Yamayoshi S, Iizuka S, Yamahsita T, Muzuta K, Okamoto M, Nishimura H, Sanjoh S, Katsushima N, Itagaki T, Nagai Y, Fujii K, Koike S
    • Journal Title

      Journal of Virology

      Volume: 86 Pages: 5686-5696

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] エンテロウイルス71の受容体としてのScavenger receptor B22012

    • Author(s)
      小池智
    • Journal Title

      The Lipid

      Volume: 23 Pages: 354-389

    • Related Report
      2012 Annual Research Report
  • [Journal Article] The Toll-like receptor 3-mediayed antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice2012

    • Author(s)
      Abe, Y., K.Fujii, N.Nagata, O.Takeuchi, S.Akira, H.Oshiumi, M.Matsumoto, T.Seya, S.Koike
    • Journal Title

      J.Virol

      Volume: 86 Issue: 1 Pages: 185-194

    • DOI

      10.1128/jvi.05245-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 712012

    • Author(s)
      McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Koike S, Kroes AC, Lukashev A, Perera D, Roivainen M, Susi P, Trallero G, Evans DJ, Simmonds P
    • Journal Title

      Journal of Virology

      Volume: 86 Issue: 5 Pages: 2676-2685

    • DOI

      10.1128/jvi.06065-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scavenger receptor B2 as a receptor for hand, foot, and mouth disease and severe neurological diseases2012

    • Author(s)
      Yamayoshi S, Fujii K, Koike S
    • Journal Title

      Frontiers in Virology

      Volume: 3 Pages: 32-32

    • DOI

      10.3389/fmicb.2012.00032

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of the Human SCARB2 Region That Is Important for Enterovirus 71 Binding and Infection2011

    • Author(s)
      Yamayoshi S, Koike S
    • Journal Title

      Journal of Virology

      Volume: 85 Issue: 10 Pages: 4937-4936

    • DOI

      10.1128/jvi.02358-10

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The TLR3-TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection.2011

    • Author(s)
      Oshiumi, H., M. Okamoto, K. Fujii, T. Kawanishi, M. Matsumoto, S. Koike, and T. Seya.
    • Journal Title

      J. Immunol.

      Volume: 187 Issue: 10 Pages: 5320-5327

    • DOI

      10.4049/jimmunol.1101503

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] EV71の非神経組織での増殖はI型インターフェロンにより抑制されている2014

    • Author(s)
      藤井健、小池智
    • 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(神奈川県横浜市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of type III interferon in intranasal infection of poliovirus in PVR transgenic mice.2014

    • Author(s)
      小池智、藤井健、Tanel Mahlakoiv, Peter Staeheli, 永田典代
    • 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(神奈川県横浜市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] エンテロウイルス71の感染初期過程解析2014

    • Author(s)
      大岡静衣、松浦絵里、小笠原勝利、石田欣二、藤井健、萩原恭二、花木賢一、Pele Choi-Sing Chong, 小池智
    • 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(神奈川県横浜市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] エンテロウイルス71受容体による種特異的、組織特異的感染の制御機構2014

    • Author(s)
      小池智
    • Organizer
      87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Enterovirus 71 –an emerging enterovirus-2014

    • Author(s)
      Koike S
    • Organizer
      The XVIII th Meeting of the European Study Group on the Molecular Biology of Picornaviruses (EUROPIC 2014)
    • Place of Presentation
      Belgium
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Role of type III Interferons in mucosal infection of poliovirus in PVR transgenic mice2014

    • Author(s)
      Koike S, Fujii K, Mahlakoiv T, Staeheli P, Nagata N
    • Organizer
      The XVIII th Meeting of the European Study Group on the Molecular Biology of Picornaviruses (EUROPIC 2014)
    • Place of Presentation
      Belgium
    • Related Report
      2013 Annual Research Report
  • [Presentation] エンテロウイルス71受容体の解析2013

    • Author(s)
      小池 智
    • Organizer
      第61回日本ウイルス学会学術集会シンポジウム
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ポリオウイルスの神経指向性のメカニズム2013

    • Author(s)
      小池 智
    • Organizer
      第18回日本神経感染症学会学術集会シンポジウム
    • Place of Presentation
      宮崎市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] SCARB2-transgenic mouse model for the study of enterovirus 71 pathogenesis2013

    • Author(s)
      Fujii K, Koike S
    • Organizer
      The XIIth Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional analyses of Scavenger receptor B2 as a receptor for Enterovirus 712012

    • Author(s)
      Yamayoshi S, Fujii K, Koike S
    • Organizer
      The XVIIth Meeting of the European Study Group on the Molecular Biology of Picornaviruses (EUROPIC 2012)
    • Place of Presentation
      Saint-Raphael, France
    • Related Report
      2012 Annual Research Report
  • [Presentation] Establishment of a transgenic mouse model for EV71 infection2012

    • Author(s)
      Fujii K, Nagata N, Yamayoshi S, Shimanuki M, Shitara H, Taya C, Koike S
    • Organizer
      XVIIth Meeting of the European Study Group on the Molecular Biology of Picornaviruses (EUROPIC 2012)
    • Place of Presentation
      Saint-Raphael, France
    • Related Report
      2012 Annual Research Report
  • [Presentation] 2つのエンテロウイルス71受容体SCARB2とPSGL1の機能比較2012

    • Author(s)
      山吉誠也、大岡静衣、藤井健、小池智
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪市
    • Related Report
      2012 Annual Research Report
  • [Presentation] EV71感受性マウスモデルの作出と解析2012

    • Author(s)
      藤井健、永田典代、山吉誠也、島貫碧、設楽浩志、多屋長治、小池智
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Scavenger receptor B2 is a receptor for Enterovirus 71.2012

    • Author(s)
      Koike S, Yamayoshi S, Fuiji K
    • Organizer
      The XIth Awaji International Forum on Infection and Immunity.
    • Place of Presentation
      Awaji, Hyogo
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Scavenger receptor B2-transgenic mouse model for EV71 infection.2012

    • Author(s)
      Koike S
    • Organizer
      International Conference on Dengue and Emerging Infection.
    • Place of Presentation
      Singapore
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Human SCARB2-dependent infection of clinical isolates of coxsackievirus A14, A16 and Enterovirus 712011

    • Author(s)
      Yamayoshi S, Iizuka S, Yamashita T, Minagawa H, Sanjoh K, Kasushima N, Itagaki, T, Mizuta K, Nagai Y, Okamoto M, Nishimura H, Fujii K, Koike S
    • Organizer
      The XVth International Congress of Virology
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Book] ウイルスーミクロの賢い寄生体ー2014

    • Author(s)
      Dorothy H. Crawford著 永田恭介監訳
    • Total Pages
      240
    • Publisher
      丸善出版
    • Related Report
      2013 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
      2014 Annual Research Report
  • [Remarks] 東京都医学総合研究所ホームページ-プロジェクト研究/ウイルス感染

    • URL

      http://www.igakuken.or.jp/research/project/res_prj17.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 公益財団法人東京都医学総合研究所公式サイト

    • URL

      http://www.igakuken.or.jp/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 公益財団法人東京都医学総合研究所公式サイト内 ウイルス感染プロジェクトホームページ

    • URL

      http://www.igakuken.or.jp/research/project/res_prj17.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/neurovirology/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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