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Development of murine model for dengue virus infection

Research Project

Project/Area Number 23590542
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionOsaka University

Principal Investigator

KUROSU TAKESHI  大阪大学, 微生物病研究所, 招へい教員 (70432432)

Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsデングウイルス / 熱帯感染症 / 蚊媒介性疾患 / 新興・再興感染症 / ウイルス / 感染症 / 動物モデル / 出血熱 / 血漿漏出 / マウスモデル / フラビウイルス / 振興・再興感染症
Outline of Final Research Achievements

The mechanism of severe dengue remains unknown, and there is no effective drug or therapy against dengue virus infection. To understand the mechanism of severe dengue, we established the mouse model system using the recombinant chimeric dengue virus and interferon knock out mice. Mice infected with the chimeric dengue virus showed plasma leakage, thrombocytopenia and antibody-dependent enhancement which have been seen in patients with severe dengue. Tumor necrosis factor (TNF) alpha was a critical factor for severe diseases. In addition, we observed strong bone marrow suppression, which is related to thrombocytopenia.
We examined if this model could be applied to study the therapeutic effect and side effect of anti-dengue virus antibody. This model is a valid model system to study pathogenesis of severe dengue and development of therapeutics.

Report

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

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] Isolation and propagation of Dengue virus in Vero and BHK-21 cells expressing human DC-SIGN stably.2014

    • Author(s)
      Phanthanawiboon S, A-nuegoonpipat A, Panngarm N, Limkittikul K, Ikuta K, Anantapreecha S, Kurosu T.
    • Journal Title

      J Virol Methods.

      Volume: 209 Pages: 55-61

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A highly conserved region between amino acids 221 and 266 of dengue virus non-structural protein 1 is a major epitope region in infected patients.2014

    • Author(s)
      Omokoko MD, Pambudi S, Phanthanawiboon S, Masrinoul P, Setthapramote C, Sasaki T, Kuhara M, Ramasoota P, Yamashita A, Hirai I, Ikuta K, Kurosu T.
    • Journal Title

      Am J Trop Med Hyg.

      Volume: 91 Issue: 1 Pages: 146-155

    • DOI

      10.4269/ajtmh.13-0624

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sequence Variation of Dengue Type 2 Virus from clinical cases in Thailand. Japanese Journal of Infectious Diseases.2014

    • Author(s)
      Kurosu T, Chaichana P, Phanthanawiboon S, Khamlert C, Yamashita A, A-nuegoonpipat A, Anantapreecha S, Ikuta K.
    • Journal Title

      Jpn J Infect Dis

      Volume: 67 Pages: 132-134

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serotype-Specific Anti-Dengue Virus NS1 Mouse Antibodies Cross-React with prM and Are Potentially Involved in Virus Production.2013

    • Author(s)
      Masrinoul P, Omokoko MD, Pambudi S, Ikuta K, Kurosu T
    • Journal Title

      Viral Immunology

      Volume: 26 Issue: 4 Pages: 250-258

    • DOI

      10.1089/vim.2012.0102

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serotype-specific anti-dengue virus NS1 mouse antibodies cross-react with prM and are potentially involved in virus production2013

    • Author(s)
      Masrinoul P., Omokoko M.D., Pambudi S., Ikuta K., and Kurosu T.
    • Journal Title

      Viral Immunology

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Platelet Apoptosis and Apoptotic Platelet Clearance by Macrophages in Secondary Dengue Virus Infections.2012

    • Author(s)
      Alonzo, M., Lacuesta, T., Dimaano, EM., Kurosu, T., Suarez, LC., Mapua, CA Akeda, Y., Matias, RR., Kuter, DJ., Nagata, S., Natividad, FF. and Oishi, K.
    • Journal Title

      J Infect Dis.

      Volume: 205 Issue: 8 Pages: 1321-1329

    • DOI

      10.1093/infdis/jis180

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quasispecies of dengue virus.2011

    • Author(s)
      Kurosu T
    • Journal Title

      Trop. Med. Health.

      Volume: 39 Pages: 1-8

    • NAID

      10030727226

    • Related Report
      2011 Research-status Report
  • [Journal Article] Co-existence of major and minor viral populations from two different origins in patients secondarily infected with dengue virus serotype 2 in Bangkok2011

    • Author(s)
      Puiprom O., Yamashita A., Sasayama M., Limkittikul K., Boonha K., Jittmitraphap A., Leaungwutiwong P,. Kurosu T., Ramasoota P., Ikuta K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 413 Issue: 1 Pages: 136-142

    • DOI

      10.1016/j.bbrc.2011.08.069

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Highly conserved region 141-168 of the NS1 protein is a new common epitope region of dengue virus.2011

    • Author(s)
      Masrinoul P, Diata MO, Pambudi S, Limkittikul K, Ikuta K, Kurosu T.
    • Journal Title

      Jpn J Infect Dis.

      Volume: 64 Pages: 109-115

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] デングウイルス/日本脳炎ウイルスによる抗体依存性感染増強効果の解析2014

    • Author(s)
      黒須 剛, 浅井あづさ, 花原景子, Supranee Phanthanawiboon, Surapee Anantapreecha, Kriengsak Limkittikul, 生田和良
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of Anti-Dengue Virus Envelope Antibody IgG subclass on Neutralizing, Virus Enhancement Activities and Protection in Mice2014

    • Author(s)
      Ririn Ramadhany, 平井到, 佐々木正大, 小野健一郎, Pongrama Ramasoota, 生田和良, 黒須 剛
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Characterization of dengue virus, the protein responsible for replication and viral pathogenesis in mouse model2014

    • Author(s)
      Supranee Phanthanawiboon, Sabar Pambudi, Magot Omokoko Diata, Panjaporn Chaichana, Chidchanok Khamlert, Surapee Anantapreecha, 生田和良, 黒須 剛
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-09 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] デング/日本脳炎キメラウイルスを用いたマウスへの感染性の解析2013

    • Author(s)
      黒須 剛
    • Organizer
      第48回日本脳炎ウイルス生態学研究会
    • Place of Presentation
      神奈川
    • Related Report
      2013 Research-status Report
  • [Presentation] MOUSE MODEL FOR DENGEU VIRUS INFECTION AND EVALUATION OF THERAPEUTICS2013

    • Author(s)
      Takeshi Kurosu
    • Organizer
      The Third International Conference on Dengue and Dengue Haemorrhagic Fever
    • Place of Presentation
      バンコク
    • Related Report
      2013 Research-status Report
  • [Presentation] 哺乳類細胞における高増殖性DENV/JEVキメラウイルス作製の試み2013

    • Author(s)
      花原景子、Sabar Pumbudi、Supranee phanthanawiboon、Magot Omokoko、浅井あづさ、生田和良、黒須剛
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] デング/日本脳炎キメラウイルスを用いたマウスへの感染性の解析2013

    • Author(s)
      黒須剛、浅井あづさ、花原景子、Chidchanok Khamlert、Sabar Pambudi、Supranee Phanthanawiboon、Magot Omokoko Diata、 Surapee Anantapreecha、生田和良
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of A New Murine model of Dengue Virus Infection.2013

    • Author(s)
      Takeshi Kurosu, Azusa Asai, Keiko Hanabara, Supranee Phanthanawiboon, Sabar Pambudi, Magot D. Omokoko, Tadahiro Sasaki, Motoki Kuhara, Pongraman Ramasoota, Kazuyoshi Ikuta
    • Organizer
      The Joint International Tropical Medicine Meeting 2013
    • Place of Presentation
      バンコク
    • Related Report
      2013 Research-status Report
  • [Presentation] Infection of dengue virus and Japanese encephalitis virus in mice.2013

    • Author(s)
      黒須 剛
    • Organizer
      Asian African Research Forum
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 治療法開発のためのデングウイルス感染マウスモデル2012

    • Author(s)
      黒須 剛
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] デングウイルス/日本脳炎ウイルスキメラウイルスを用いたマウスへの感染性の解析2012

    • Author(s)
      黒須 剛
    • Organizer
      第47回日本脳炎ウイルス生態学研究会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] Infection of mouse cells with dengue virus and Japanese encephalitis virus2012

    • Author(s)
      Takeshi Kurosu, Sabar Pambudi, Omokoko Magot, Chidchanok Khamlert, Supranee Phanthanawiboon1, and Kazuyoshi Ikuta
    • Organizer
      Asian African Research Forum on Emerging and Reemerging Infections 2012
    • Place of Presentation
      Kobe
    • Related Report
      2011 Research-status Report
  • [Presentation] Infection of mouse cells with dengue virus and Japanese encephalitis virus.2011

    • Author(s)
      黒須 剛、Sabar Pambudi, Omokoko Magot, Chidchanok Khamlert、Supranee Phanthanawiboon、Surapee Anantapreecha, 生田和良
    • Organizer
      第59回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Remarks] 大阪大学微生物用研究所ウイルス免疫分野

    • URL

      http://virology.biken.osaka-u.ac.jp/dengue-j.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 大阪大学微生物病研究所 ウイルス免疫分野 デング

    • URL

      http://virology.biken.osaka-u.ac.jp/dengue.php

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://virology.biken.osaka-u.ac.jp/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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