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Struggle between host defense and viral escape mechanisms

Research Project

Project/Area Number 16K08260
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Fukasawa Masayoshi  国立感染症研究所, 細胞化学部, 室長 (20291130)

Research Collaborator Shirasago Yoshitaka  
Shimizu Yoshimi  
Ogawa Motohiko  
Suzuki Takeru  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsC型肝炎ウイルス / 受容体 / 宿主細胞 / モノクローナル抗体 / HCV / ウイルス / ノックアウト細胞
Outline of Final Research Achievements

We have developed many kinds of useful tools for analyzing hepatitis C virus (HCV) entry mechanisms, such as viral receptor-defective cell lines, anti-viral receptor monoclonal antibodies, and highly infectious HCV strains. In this project, using these tools, we isolated HCV-JFH1 sub-strains having different host receptor-dependency. We also showed that one isolated sub-strain uses new host molecule as its entry receptor. It seemed that these phenotypes of sub-strains can be acquired by only one amino acid mutation.

Academic Significance and Societal Importance of the Research Achievements

特定のC型肝炎ウイルス(HCV)受容体に非依存性を獲得したHCV変異亜株が(比較的簡便に)分離されることを示し、そのメカニズムの一端を明らかにした。以上の成果は、宿主-ウイルス間の攻防の分子基盤の進化を考える上で、学術的意義は大きいと考えている。また、受容体の選択性が変わることで、肝臓以外に感染する能力を獲得しうることから、依然として不明の点の多い、HCVによる肝外病変の発症メカニズムを考えるヒントとなる可能性があり、医学的な見地からも意義があるかもしれない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Journal Article] Inhibition Mechanisms of Hepatitis C Virus Infection by Caffeic Acid and Tannic Acid2019

    • Author(s)
      Shirasago Yoshitaka、Inamori Yoko、Suzuki Takeru、Tanida Isei、Suzuki Tetsuro、Sugiyama Kazuo、Wakita Takaji、Hanada Kentaro、Fukasawa Masayoshi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 5 Pages: 770-777

    • DOI

      10.1248/bpb.b18-00970

    • NAID

      130007641446

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-05-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-hepatitis C Virus Strategy Targeting the Entry Steps2019

    • Author(s)
      Fukasawa Masayoshi
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 1 Pages: 89-95

    • DOI

      10.1248/yakushi.18-00164-5

    • NAID

      130007541657

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monoclonal Antibodies against Occludin Completely Prevented Hepatitis C Virus Infection in a Mouse Model2018

    • Author(s)
      Shimizu Yoshimi、Shirasago Yoshitaka、Kondoh Masuo、Suzuki Tetsuro、Wakita Takaji、Hanada Kentaro、Yagi Kiyohito、Fukasawa Masayoshi
    • Journal Title

      Journal of Virology

      Volume: 92 Issue: 8

    • DOI

      10.1128/jvi.02258-17

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro2018

    • Author(s)
      Ogawa M, Shirasago Y, Ando S, Shimojima M, Saijo M, Fukasawa M
    • Journal Title

      J Infect Chemother

      Volume: 印刷中 Issue: 8 Pages: 597-601

    • DOI

      10.1016/j.jiac.2018.03.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thermostable hepatitis C virus JFH1-derived variant isolated by adaptation to Huh7.5.1 cells2018

    • Author(s)
      Shirasago Yoshitaka、Fukazawa Hidesuke、Aizaki Hideki、Suzuki Tetsuro、Suzuki Takeru、Sugiyama Kazuo、Wakita Takaji、Hanada Kentaro、Abe Ryo、Fukasawa Masayoshi
    • Journal Title

      Journal of General Virology

      Volume: 99 Issue: 10 Pages: 1407-1417

    • DOI

      10.1099/jgv.0.001117

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection2016

    • Author(s)
      Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Ryosuke Suzuki, Kazuo Sugiyama, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 5 Pages: 839-848

    • DOI

      10.1248/bpb.b15-01023

    • NAID

      130005149248

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Host cholesterol biosynthesis as a potential target for anti-hepatitis C virus strategies2016

    • Author(s)
      Saito K, Fukasawa M
    • Journal Title

      Seikagaku

      Volume: 88 Pages: 411-415

    • NAID

      40020895315

    • Related Report
      2016 Research-status Report
  • [Presentation] HCV侵入過程の基礎研究から感染防御・予防・治療の応用研究へ2018

    • Author(s)
      深澤 征義
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HCV侵入機構とその感染予防・治療薬への応用2018

    • Author(s)
      深澤 征義
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HCV侵入過程の基礎研究から感染防御・予防・治療の応用研究へ2018

    • Author(s)
      深澤征義
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] C型肝炎ウイルス感染におけるOccludin分子の重要性~Occludinノックアウトヒト肝培養細胞を用いた検討2016

    • Author(s)
      深澤 征義、白砂 圭崇、清水 芳実、谷田以誠、近藤 昌夫、八木 清仁、鈴木 哲朗、鈴木亮介、杉山和夫、脇田 隆字、花田 賢太郎
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Occludin-knockout human hepatic cells are non-permissive to hepatitis C virus infection2016

    • Author(s)
      Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Ryosuke Suzuki, Kazuo Sugiyama, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
    • Organizer
      RNA2016
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-06-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 国立感染症研究所細胞化学部第三室

    • URL

      https://www.niid.go.jp/niid/ja/from-biochem/911-3rd.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 細胞化学部 第三室

    • URL

      https://www.niid.go.jp/niid/ja/from-biochem/911-3rd.html

    • Related Report
      2017 Research-status Report
  • [Remarks] オクルディン分子の発現が欠損したヒト肝由来細胞ではC型肝炎ウイルスの感染が見られなくなる

    • URL

      https://www.niid.go.jp/niid/ja/basic-science/466-biochemistory/6502-biochem-2016-1.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-01-27  

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