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Establishment ofpredidive method for shift of coreceptor usage in HIV 1-infected individnals

Research Project

Project/Area Number 18590533
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionKumamoto University

Principal Investigator

MAEDA Yosuke  Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Associate Professor (30284764)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsVirus / Translational research / HIV / Coreceptor / エンベロープ / V3
Research Abstract

The disease progression of HIV-1 infection is largely associated with a switch of coreceptor usage by HIV-1 from CCR5 to CXCR4. Although most of CXCR4-using viruses retain CCR5 usage called R5X4 viruses, the replication of R5X4 viruses were inhibited by CXCR4 inhibitors alone in the cells expressing both CCR5 and CXCR4, indicating the preferential usage of CXCR4 by these viruses. In order to determine which regions of the Env are associated with the preferential usage of CXCR4, we isolated an escape mutant in the presence of a CXCR4 antagonist T140 from an R5X4 virus (89.6 strain). An isolated T140-escape mutant harbored a single amino acid substitution in the V3 region of gp120(Arginine to Serine, R308S). Luciferase-reporter HIV-1 pseudotyped with the mutant Env showed that the substitution totally conferred resistance to CXCR4 antagonists but increased sensitivity to a CCR5 antagonist TAK-779 in the infection of the cells expressing both CCR5 and CXCR4, indicating the preferential usage of CCR5. Analyses using the cells expressing a single coreceptor showed that the mutant Env predominantly and efficiently utilized CCR5 than CXCR4 with retaining R5X4 phenotype. These results indicated that the preferential usage of CXCR4 by the R5X4 virus was determined by the single amino acid in the V3 region of gp120.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (12 results)

All 2008 2007 2006

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (3 results)

  • [Journal Article] Neutralizing antibodies decrease the envelope fluidity of HIV-12008

    • Author(s)
      Harada, S.
    • Journal Title

      Virology 282

      Pages: 142-150

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Altered sensitivity of an R5X4 HIV-1 strain 89.6 to coreceptor inhibitors by asingle amino acid substitution in the V3 region of gp1202008

    • Author(s)
      Maeda, Y.
    • Journal Title

      Antiviral Res. 77

      Pages: 128-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Altered sensitivity of an R5X4 HIV-1 strain 89.6 to coreceptor inhibitors by a single amino acid substitution in the V3 region of gp1202008

    • Author(s)
      Maeda, Y.
    • Journal Title

      Antiviral Res 77

      Pages: 128-135

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Neutralizing antibodies decrease the envelope fluidity of HIV-1.2008

    • Author(s)
      Harada, S.
    • Journal Title

      Virology 282

      Pages: 142-150

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Altered sensitivity of an R5X4 HIV-1 strain 89.6 to coreceptor inhibitors by a single aminoacid substitution in the V3 region of gp120.2008

    • Author(s)
      Maeda, Y.
    • Journal Title

      Antiviral Res. 77

      Pages: 128-135

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virionincoraorated CCR52007

    • Author(s)
      Monde, K.
    • Journal Title

      J.Biol.Chem. 207

      Pages: 36923-36932

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virion incorporated CCR5.2007

    • Author(s)
      Monde, K.
    • Journal Title

      J. Biol. Chem 207

      Pages: 36923-36932

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gp120 V3-dependent impairment of R5 HIV-1 infectivity due to virion incorporated CCR5.2007

    • Author(s)
      Monde, K.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 36923-36932

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistance profile of a neutralizing anti-HIV monoclonal antibody, KD-247, that shows favourable synergism with anti-CCR5 inhibitors.2006

    • Author(s)
      Yoshimura K, Shibata J, Kimura T, Honda A, Maeda Y, Koito A, Murakami T, Mitsuya H, Matsushita S
    • Journal Title

      AIDS 20(16)

      Pages: 2065-2073

    • Related Report
      2006 Annual Research Report
  • [Presentation] ヒトT細胞株のHIV-1感受性の解析2007

    • Author(s)
      前田 洋助
    • Organizer
      第55回日本ウイルス学会学術集会総会
    • Place of Presentation
      札幌コンベンションセンタ
    • Year and Date
      2007-10-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] CXCR4 antagonist-induced coreceptor switch from X4 to R5 phenotype in vitro determined by a single amino acid substitution in the V3 region of human immunode ficiency virus tune 1 gp1202006

    • Author(s)
      Maeda, Y.
    • Organizer
      XVI International AIDS Conference
    • Place of Presentation
      Metro Toronto Convention Centre,Toronto,Canada
    • Year and Date
      2006-08-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CXCR4 antagonist-induced coreceptor switch from X4 to R5 phenotype in vitro determined by a single amino acid substitution in the V3 region of human immunodeficiency virus type 1 gp1202006

    • Author(s)
      Yosuke, Maeda
    • Organizer
      XVI International AIDS Conference
    • Place of Presentation
      Toronto Canada
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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