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Systems Virology for understanding viral pathogenesis

Research Project

Project/Area Number 16KT0111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Complex Systems Disease Theory
Research InstitutionKyoto University

Principal Investigator

Noda Takeshi  京都大学, ウイルス・再生医科学研究所, 教授 (00422410)

Co-Investigator(Kenkyū-buntansha) 佐藤 佳  東京大学, 医科学研究所, 准教授 (10593684)
渡士 幸一  国立感染症研究所, ウイルス第二部, 主任研究官 (40378948)
岩見 真吾  九州大学, 理学研究院, 准教授 (90518119)
Project Period (FY) 2016-07-19 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords数理解析 / エボラウイルス / C型肝炎ウイルス / ヒト免疫不全ウイルス / HIV / ウイルス / ウイルス感染症 / ウイルス学
Outline of Final Research Achievements

By combining experiments and mathematical modeling, we try to understand Ebola virus pathogenesis, human immunodeficient virus replication mechanism, and antiviral effects against Hepatitis B virus quantitatively. We obtained data set including virus titers, the amount of cytokines and chemokines, viral genome sequences, and so on, and analyzed them by mathematics. We found several important host factors involved in Ebola virus pathogenesis and Human immunodeficiency virus replication in vivo. In addition, we found proper combination of three antiviral drugs against Hepatitis B virus that decreases the emergence of the antiviral-resistant virus.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、数理科学的な解析を駆使する事で統合的視点からウイルス感染というシステム全体を眺め、病態の発症や薬剤の効果を体系的に理解できる点にある。これらの研究を通じて、実験科学で得られた成績(例:感染個体におけるウイルス増殖機構や重症度など)に新たな意味や価値を付加することができた。いくつかの実験データを基に開発した数理モデルを用いて、最適な組み合わせの抗ウイルス薬を予測し、実際に耐性ウイルスの出現頻度が少ない薬剤の組み合わせを見出すことにも成功した。

Report

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

    (12 results)

All 2019 2018 2017 2016

All Journal Article (12 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results)

  • [Journal Article] Epidermal growth factor receptor is a host entry cofactor triggering hepatitis B virus internalization2019

    • Author(s)
      M. Iwamoto, W. Saso, R. Sugiyama, K. Ishii, M. Ohki, S. Nagamori, R. Suzuki, H. Aizaki, A. Ryo, J-H Yun, S-Y Park, N. Ohtani, M. Muramatsu, S. Iwami, Y. Tanaka, C. Sureau, T. Wakita and K. Watashi
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 116 Issue: 17 Pages: 8487-8492

    • DOI

      10.1073/pnas.1811064116

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Defect in Influenza A Virus Particle Assembly Specific to Primary Human Macrophages.2018

    • Author(s)
      Bedi S, Noda T, Kawaoka Y, Ono A.
    • Journal Title

      MBio

      Volume: 9 Issue: 5

    • DOI

      10.1128/mbio.01916-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cryo-EM structure of the Ebola virus nucleoprotein-RNA complex at 3.6 A resolution.2018

    • Author(s)
      Sugita Y, Matsunami H, Kawaoka Y, Noda T, Wolf M.
    • Journal Title

      Nature

      Volume: 563 Issue: 7729 Pages: 137-140

    • DOI

      10.1038/s41586-018-0630-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.2018

    • Author(s)
      Mahgoub M, Yasunaga JI, Iwami S, Nakaoka S, Koizumi Y, Shimura K, Matsuoka M.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Issue: 6 Pages: 529-538

    • DOI

      10.1073/pnas.1715724115

    • NAID

      120006697286

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human-specific adaptations in Vpu conferring anti-tetherin activity are critical for efficient early HIV-1 replication in vivo.2017

    • Author(s)
      Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter & Kei Sato
    • Journal Title

      Cell Host & Microbe

      Volume: 23 Issue: 1 Pages: 110-120

    • DOI

      10.1016/j.chom.2017.12.009

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments.2017

    • Author(s)
      Ohashi HK, Koizumi Y, Fukano K, Wakita T, Perelson AS, Iwami S, Watashi K
    • Journal Title

      Proc Acad Natl Acad USA

      Volume: 114 Issue: 23

    • DOI

      10.1073/pnas.1705234114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation.2017

    • Author(s)
      Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi & Kei Sato
    • Journal Title

      PLOS Pathogens

      Volume: 13 Issue: 5 Pages: 31-31

    • DOI

      10.1371/journal.ppat.1006348

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection2017

    • Author(s)
      Koizumi Y, Ohashi H, Nakajima S, Tanaka Y, Wakita T, Perelson AS, Iwami S, Watashi K
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114(8) Issue: 8 Pages: 1922-1927

    • DOI

      10.1073/pnas.1610197114

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy2017

    • Author(s)
      CA. Beauchemin, T. Miura, S. Iwami
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 42765-42765

    • DOI

      10.1038/srep42765

    • NAID

      120005997746

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modelling Ebola virus dynamics: Implications for therapy.2016

    • Author(s)
      Martyushev A, Nakaoka S, Sato K, Noda T, Iwami S.
    • Journal Title

      Antiviral Res

      Volume: 135 Pages: 62-73

    • DOI

      10.1016/j.antiviral.2016.10.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model2016

    • Author(s)
      Ikeda H, Nakaoka S, de Boer RJ, Morita S, Misawa N, Koyanagi Y, Aihara K, Sato K, Iwami S
    • Journal Title

      Retrovirology

      Volume: 13 Issue: 1 Pages: 23-23

    • DOI

      10.1186/s12977-016-0252-2

    • NAID

      120006353849

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Validating experimentally derived knowledge about influenza A defective interfering particles.2016

    • Author(s)
      Liao LE, Iwami S, Beauchemin CA.
    • Journal Title

      J R Soc Interface.

      Volume: 13 Pages: 124-124

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant

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Published: 2016-07-20   Modified: 2023-03-08  

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