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Impact of HIV infection pathway on the potency of antiviral agents

Research Project

Project/Area Number 24791021
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Infectious disease medicine
Research InstitutionKyoto University

Principal Investigator

SHIMURA Kazuya  京都大学, ウイルス研究所, 助教 (90613836)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsHIV / 抗ウイルス薬 / 感染経路
Research Abstract

HIV infects target cells by two pathways, cell-free infection and cell-to-cell transmission. In cell-free infection, HIV virions present in the intercellular space infect target cells, while in cell-to-cell transmission, HIV is transmitted from infected to uninfected cells through cellular gap. To analyze the effect of infection pathways on drug susceptibility, we established an assay system, in which HIV-1 carrying a fluorescent protein gene, and a cell-labeling dye were utilized for precise quantification of HIV-1-infected cells under cell-free infection and cell-to-cell transmission separately. Using this system, inhibitory activity of anti-HIV drugs targeting several replication steps was evaluated. Overall, weak anti-HIV activity of tested drugs under the cell-to-cell pathway compared to the cell-free pathway with several-fold ranges, was observed. Taken together, infection pathway of HIV affects the activity of anti-HIV drugs.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (6 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Structure-activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents2013

    • Author(s)
      Mizuhara T, Kato T, Hirai A, Kurihara H, Shimada Y, Taniguchi M, Maeta M, Togami H, Shimura K, Matsuoka M, Okazaki S, Takeuchi T, Ohno H, Oishi S, Fujii N.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 23 Issue: 16 Pages: 4557-4561

    • DOI

      10.1016/j.bmcl.2013.06.026

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains.2013

    • Author(s)
      Kazuki Shimane, KumiKawaji, Fusako Miyamoto, Shinya Oishi, Kentaro Watanabe, YasukoSakagami, Nobutaka Fujii, Kazuya Shimura, Masao Matsuoka, Mitsuo Kaku, Stefan Sarafianos, and Eiichi Kodama
    • Journal Title

      Antimicrobal Agents and Chemotherapy

      Volume: 57 Issue: 8 Pages: 4035-4038

    • DOI

      10.1128/aac.00237-13

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of biotin- or alkyne-conjugated photoaffinity probes for studying the target molecules of PD 4041822013

    • Author(s)
      Tsukasa Mizuhara, Shinya Oishi, Hiroaki Ohno, Kazuya Shimura, Masao Matsuoka, Nobutaka Fujii
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21 Issue: 7 Pages: 2079-2087

    • DOI

      10.1016/j.bmc.2013.01.016

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents2013

    • Author(s)
      Tognmi, H., Shimura, K., Okamoio, M., Yoshikawa, R., MiyazHwa, T., Matsuoka M.
    • Journal Title

      Journal of Virology

      Volume: 87 Issue: 8 Pages: 4322-4329

    • DOI

      10.1128/jvi.03208-12

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design.2013

    • Author(s)
      Izumi K, Kawaji K, Miyamoto F, Shimane K, Shimura K, Sakagami Y, Hattori T, Watanabe K, Oishi S, Fujii N, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN.
    • Journal Title

      Int J Biochem Cell Biol.

      Volume: 45 Issue: 4 Pages: 908-915

    • DOI

      10.1016/j.biocel.2013.01.015

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCR4 stimulates macropinocytosis: implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV2012

    • Author(s)
      Gen Tanaka, Ikuhiko Nakase, et al.
    • Journal Title

      Chemistry & Biology

      Volume: 19 Issue: 11 Pages: 1437-1446

    • DOI

      10.1016/j.chembiol.2012.09.011

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure-activity relationship study of pyrimido[1, 2-c][1,3]benzothiazin-6-imine derivatives for potent anti-HIV agents.2012

    • Author(s)
      Tsukasa Mizuhara, Shinya Oishi, Hiroaki Ohno, Kazuya Shimura, Masao Matsuoka, Nobutaka Fujii
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 20 Issue: 21 Pages: 6334-6441

    • DOI

      10.1016/j.bmc.2012.08.030

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Concise synthesis and anti-HIV activity of pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic heterocycles.2012

    • Author(s)
      Mizuhara T, Oishi S, Ohno H, Shimura K, Matsuoka M, Fujii N.
    • Journal Title

      Org. Biomol. Chem.

      Volume: 10 Issue: 33 Pages: 6792-6802

    • DOI

      10.1039/c2ob25904d

    • NAID

      120005302103

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗ウイルス薬感受性に対するHIV感染経路の影響2013

    • Author(s)
      志村和也, 大石真也, 藤井信孝, 松岡雅雄
    • Organizer
      第27回日本エイズ学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗ウイルス薬感受性に対するHIV感染経路の影響2013

    • Author(s)
      志村和也、大石真也、藤井信孝、松岡雅雄
    • Organizer
      第27回日本エイズ学会学術集会
    • Place of Presentation
      市民会館崇城大学ホール・熊本市交際交流会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] 広範なスペクトルを有する新規抗HIV 薬の同定とその開発2012

    • Author(s)
      志村和也, 水原司, 大石真也, 藤井信孝, 松岡雅雄
    • Organizer
      第26回に日本エイズ学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] ニホンザルより検出されたSRV-4に対する抗HIV 薬の効果2012

    • Author(s)
      戸上博昭, 志村和也, 宮沢孝幸, 松岡雅雄
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] ニホンザルより検出されたSRV-4に対する抗HIV薬の効果2012

    • Author(s)
      戸上博昭、志村和也、宮沢孝幸、松岡雅雄
    • Organizer
      日本ウイルス学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 広範なスペクトルを有する新規抗HIV薬の同定とその開発2012

    • Author(s)
      志村和也、水原司、大石真也、藤井信孝、松岡雅雄
    • Organizer
      日本エイズ学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/VirusControl/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 京都大学ウイルス研究所ウイルス制御研究領域

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/VirusControl/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 京都大学ウイルス研究所

    • URL

      http://www.virus.kyoto-u.ac.jp/

    • Related Report
      2012 Research-status Report
  • [Remarks] 最新の研究成果

    • URL

      http://www.virus.kyoto-u.ac.jp/about/y2012/matsuoka201303.html

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] ピラゾール誘導体またはその塩ならびにそれらを含有する医薬組成物2013

    • Inventor(s)
      加藤貴之, 平井敦, 松岡雅雄, 志村和也
    • Industrial Property Rights Holder
      富士フイルム株式会社, 国立大学法人京都大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-092023
    • Filing Date
      2013-04-25
    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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