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A study of chemokine receptor dynamics and its inhibitor(s) in HIV infection

Research Project

Project/Area Number 26461510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionKumamoto University

Principal Investigator

Nakata Hirotomo  熊本大学, 医学部附属病院, 講師 (40628492)

Research Collaborator Maeda Kenji  
Iwami Shingo  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHIV感染症 / CCR5 / 侵入阻害薬 / HIV感染 / ケモカイン / CCR5阻害剤
Outline of Final Research Achievements

We constructed wild type CCR5(CCR5-WT) and mutant CCR5(CCR5-MT), which loses susceptibility against HIV, coexpressing cells and tested HIV infectivity using these cells.10% and 50% levels of CCR5-MT expression reduced the susceptibility against HIV by 50% and almost 100% compared with only CCR5-WT espressing cells, respectively. This result strongly suggested that multiple CCR5 are required for the HIV entry step. Next we developed a mathematical model based on the correlation between the ratio of CCR5-MT expression and HIV susceptibility, and estimated the numbers of CCR5 required for the HIV infection. As a result we quantitatively estimated 6-8 CCR5s are required for gp120 trimer-CCR5 interaction. These data revealed a part of the entry step of HIV infection.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 2013

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

  • [Journal Article] C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir2015

    • Author(s)
      Aoki, M. Hayashi, H. Yedidi, R. S. Martyr, C. D. Takamatsu, Y. Aoki-Ogata, H. Nakamura, T. Nakata, H. Das, D. Yamagata, Y. Ghosh, A. K. Mitsuya, H.
    • Journal Title

      Journal of Virology

      Volume: 90 Issue: 5 Pages: 2180-94

    • DOI

      10.1128/jvi.01829-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] EFdA, a reverse transcriptase inhibitor , potently blocks HIV -1 ex vivo infection of Langerhans cells within epithelium2014

    • Author(s)
      Matsuzawa T, Kawamura T, Ogawa Y, Maeda K, Nakata H, Moriishi K, Koyanagi Y, Gatanaga H, Shimada S, Mitsuya H
    • Journal Title

      J Invest Dermatol

      Volume: 134(4) Issue: 4 Pages: 1158-61

    • DOI

      10.1038/jid.2013.467

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Delayed emergence of HIV-1 variants resistant to 4’-ethynyl-2-fluoro-2’-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-9860012013

    • Author(s)
      Kenji Maeda, Darshan V Desai, Manabu Aoki, Hirotomo Nakata, Eiichi N Kodama, Hiroaki Mitsuya
    • Journal Title

      Antiviral Therapy

      Volume: 19 Issue: 2 Pages: 179-189

    • DOI

      10.3851/imp2697

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規CCR5阻害剤GRL-007の抗HIV活性の検討2014

    • Author(s)
      中田 浩智, Debananda Das, 前田 賢次, Kalapala Venkateswara Rao, Arun K. Ghosh, 満屋 裕明
    • Organizer
      日本エイズ学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2014-12-03 – 2014-12-05
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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