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Development of therapeutics against highly pathogenic bunyavirus infection

Research Project

Project/Area Number 18KK0232
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Shimojima Masayuki  国立感染症研究所, ウイルス第一部, 室長 (10422411)

Co-Investigator(Kenkyū-buntansha) 藤田 尚志  京都大学, ウイルス・再生医科学研究所, 客員教授 (10156870)
渡辺 俊平  岡山理科大学, 獣医学部, 准教授 (10621401)
呉 成旭  京都大学, ウイルス・再生医科学研究所, 研究員 (30817416)
竹内 文彦  京都大学, ウイルス・再生医科学研究所, 研究員 (20852437)
Project Period (FY) 2018-10-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords高病原性ブニヤウイルス感染症 / 治療 / 抗体 / 炎症メカニズム / 病原因子 / 併用 / 高病原性ブニヤウイルス / CCHF / SFTS / 新規レクチン / 治療用抗体 / 中和 / SFTSウイルス / 受容体 / mAb / 高病原性ウイルス / クリミア・コンゴ出血熱ウイルス / 重症熱性血小板減少症候群 / リフトバレー熱 / 新規治療法 / 組み換えウイルス / クリミア・コンゴ出血熱 / ウイルス受容体
Outline of Final Research Achievements

SFTS/CCHF/RVF are infectious diseases with high case fatality rates. To develop therapeutics against these diseases, we studied mainly on SFTS, which is reported in Japan annually, and obtained following achievement:
Establishment of an efficient functional screening of SFTS virus receptors, identification of virulent factors and related host factors, molecular elucidation of mechanisms in induction of cytokine storm upon SFTS virus infection, preparation of therapeutic monoclonal antibodies/nanobodies against SFTS/CCHF viral envelops and their evaluation in animal models.
Mechanisms of actions of these therapeutic candidates or targets are distinct with each other, their combination use will be useful in therapy of severe patients or prevention of disease worsening in SFTS/CCHF/RVF.

Academic Significance and Societal Importance of the Research Achievements

SFTSについて治療効果の高い治療用抗ウイルス抗体の作製戦略、感染拡大を抑制する宿主標的候補分子決定、および過剰な炎症を抑制する標的候補決定という3本柱が得られた。感染阻害と炎症抑制、(本研究では検討できなかったが)核酸アナログによるゲノム複製阻害はそれぞれ作用機序が全く異なるので、これらの併用によりSFTSの特に重症例の治療や重症化阻止が期待できると考えられた。SFTSの研究で得られた戦略が今後CCHFやRVFなど他の高病原性ブニヤウイルス感染症の治療開発を助けるものと考えている。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (5 results) Book (1 results)

  • [Int'l Joint Research] University of Bonn(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Bonn University(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ボン大学(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication2023

    • Author(s)
      Tsukamoto Y, Hiono T, Matsuno K, Igarashi M, Kato H, et al.
    • Journal Title

      Science

      Volume: 379 Issue: 6632 Pages: 586-591

    • DOI

      10.1126/science.add0875

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model2022

    • Author(s)
      Shimojima Masayuki、Sugimoto Satoko、Umekita Kunihiko、Onodera Taishi、Sano Kaori、Tani Hideki、Takamatsu Yuki、Yoshikawa Tomoki、Kurosu Takeshi、Suzuki Tadaki、Takahashi Yoshimasa、Ebihara Hideki、Saijo Masayuki
    • Journal Title

      Viruses

      Volume: 14 Issue: 8 Pages: 1665-1665

    • DOI

      10.3390/v14081665

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of Keterah orthonairovirus and evaluation of therapeutic candidates against Keterah orthonairovirus infectious disease.2022

    • Author(s)
      Sugimoto S, Suda Y, Nagata N, Fukushi S, Yoshikawa T, Kurosu T, Mizutani T, Saijo M, Shimojima M.
    • Journal Title

      Ticks Tick Borne Dis.

      Volume: 13(1) Issue: 1 Pages: 101834-101834

    • DOI

      10.1016/j.ttbdis.2021.101834

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient Functional Screening of a Cellular cDNA Library to Identify Severe Fever With Thrombocytopenia Syndrome Virus Entry Factors2020

    • Author(s)
      Shimojima M, Sugimoto S, Taniguchi S, Yoshikawa T, Kurosu T, Saijo M.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 5996-5996

    • DOI

      10.1038/s41598-020-62876-1

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Terminal Genome Sequences of the Soft Tick Bunyavirus2020

    • Author(s)
      Sugimoto S, Suda Y, Yoshikawa T, Kurosu T, Mizutani T, Saijo M, Shimojima M.
    • Journal Title

      Microbiol Resour Announc.

      Volume: 9 Issue: 18

    • DOI

      10.1128/mra.00126-20

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-cell fusion induced by reovirus FAST proteins enhances replication and pathogenicity of non-enveloped dsRNA viruses.2019

    • Author(s)
      1.Kanai Y, Kawagishi T, Sakai Y, Nouda R, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
    • Journal Title

      PLoS Pathog.

      Volume: 15 Issue: 4 Pages: e1007675-e1007675

    • DOI

      10.1371/journal.ppat.1007675

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SFTSウイルスの新規病原因子の同定2021

    • Author(s)
      下島 昌幸, 米満 研三, 網  康至, 杉元 聡子, 髙松 由基, 吉河 智城, 黒須  剛, 西條 政幸
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] ケテラオルソナイロウイルス感染症に対するファビピラビルの有効性2021

    • Author(s)
      杉元 聡子, 黒須  剛, 吉河 智城, 髙松 由基, 大場 真己, 大松  勉, 水谷 哲也, 西條 政幸, 下島 昌幸
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] A novel functional screening method to identify severe fever with thrombocytopenia syndrome virus entry factors from cDNA library.2019

    • Author(s)
      2.Shimojima M, Sugimoto S, Taniguchi S, Yoshikawa T, Kurosu T, Saijo M.
    • Organizer
      The 67th Annual Meeting of the Japanese Society for Virology.
    • Related Report
      2019 Research-status Report
  • [Presentation] Characterization of Soft tick bunyavirus isolated from ticks in Japan.2019

    • Author(s)
      1.Sugimoto S, Suda Y, Kurosu T, Yoshikawa T, Oba M, Omatsu T, Horimoto T, Mizutani T, Saijo M, Shimojima M.
    • Organizer
      The 67th Annual Meeting of the Japanese Society for Virology.
    • Related Report
      2019 Research-status Report
  • [Presentation] 重症熱性血小板減少症候群ウイルスの最新の知見2019

    • Author(s)
      下島昌幸
    • Organizer
      第71回日本衛生動物学会大会
    • Related Report
      2018 Research-status Report
  • [Book] パンデミック時代の感染症研究2021

    • Author(s)
      下島昌幸、西條政幸
    • Total Pages
      4
    • Publisher
      羊土社
    • ISBN
      9784758103923
    • Related Report
      2020 Research-status Report

URL: 

Published: 2018-10-12   Modified: 2024-01-30  

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