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Basic Research for AIDS control

Research Project

Project/Area Number 10180103
Research Category

特定領域研究

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

UCHIYAMA Takashi  京都大学, 医学研究科, 教授 (80151900)

Co-Investigator(Kenkyū-buntansha) 高折 晃史  京都大学, 医学研究科, 助手 (20324626)
MATSUSHITA Shuzo  熊本大学, エイズ学研究センター, 教授 (00199788)
KOYANAGI Yoshio  東北大学, 医学系研究科, 教授 (80215417)
MITUYA Yoshiaki  Kumamoto University, Faculty of Medicine, Professor, 医学部, 教授 (20136724)
HORI Toshiyuki  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (70243102)
永井 美之  国立感染症研究所, エイズ研究センター, センター長 (20022874)
Project Period (FY) 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥76,100,000 (Direct Cost: ¥76,100,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥18,500,000 (Direct Cost: ¥18,500,000)
Fiscal Year 2000: ¥19,500,000 (Direct Cost: ¥19,500,000)
Fiscal Year 1999: ¥18,500,000 (Direct Cost: ¥18,500,000)
Fiscal Year 1998: ¥17,300,000 (Direct Cost: ¥17,300,000)
KeywordsHIV-1 / Host Factors / Pathophysiology / Immune response / AIDS Control / Chemokine / Chemokine Receptor / エイズ / HIV複製 / コレセプター / 抗HIV免疫 / 抗HIV剤 / 薬剤耐性
Research Abstract

平成10年度より平成13年度の間、エイズ制御に向けた基礎研究を行ってきた本領域研究では、1)柱1.HIVの複製における宿主因子では、HIV-1の複製の素過程に要求される宿主側因子の同定と、それら因子とウイルスの相互作用を明らかにすることによって、HIV-1の生活環の一層深い理解をえること、2)柱2.HIV感染症の病態と免疫では、HIVに対する免疫応答機構とウイルスの持続感染成立機構、および免疫系崩壊機構を解明すること、3)柱3.エイズの予防・制御では、HIVの生活環の各ステップを標的とした、新しい抗HIV剤の開発と薬剤耐性機構を解明すること、の3つを重点目標として、エイズ病態の理解とその制御に向けた基礎研究を推進してきた。この間、ケモカインレセプターを介するHIVの細胞侵入機構の解析とその新しい制御物質の発見、ケモカイン/ケモカインレセプターとHIV感染病態、インテグレースの機能、HIVの転写機構・粘膜ワクチン開発の基礎研究、抗HIVCTLとHIV感染病態、抗HIV剤耐性機構、新しい抗HIV剤の候補物質の発見などにおいて、いくつかの注目すべき成果を挙げてきた。
平成14年度においては、本領域全体としての研究成果の取りまとめの活動として、1)引き続き、各研究者間の緊密な連係を進め、試料交換、共同研究の推進を行い、さらに、エイズ研究に関する国内外の情報収集と関連研究者への情報提供を行った。
2)本領域研究班全体の研究成果が広く社会に還元されるよう、本領域研究班の研究成果の取りまとめの冊子を出版した。

Report

(6 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Ichiyama K.: "A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity"Proc. Natl. Acad. Sic. USA. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yonezawa A.: "Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells"J. Virol.. 77(6). 3777-3784 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miura Y.: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection"Proc. Natl. Acad. Sci. USA. 100(5). 2777-2782 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yonezawa A.: "Replacement of the V3 Region of gp120 with SDF-1 Preserves the Infectivity of T-Cell Line-Tropic Human Immunodeficiency Virus Type 1"J. Virol.. 75(9). 4258-4267 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura T.: "Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeficiency virus during highly active antiretroviral therapy"J. Infect. Dis.. 185(1). 53-60 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang FX.: "Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type 1-infected patients undergoing highly active antiretroviral therapy"J. Infect. Dis.. 185(5). 608-617 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yonezawa A.: "Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type I with Alpha Interferon Production and Maturation into Dendritic Cells"J.Virol.. 77(6). 3777-3784 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa A.: "Replacement of the V3 Region of gp12O with SDF-1 Preserves the Infectivity of T-Cell Line-Tropic Human Immunodeficiency Virus Type 1"J.Virol.. 75(9). 4258-4267 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichiyama K.: "A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity"Proc.Natl.Acad.Sci. USA. 100(7). 4185-4190 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura Y.: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection"Proc.Natl.Acad.Sci. USA. 100(5). 2777-2782 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura T.: "Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeticiency virus during highly active antiretroviral therapy"J.Infect.Dis.. 185(1). 53-60 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gatanada H.: "Amino acid substitutions in non-cleavage sites of the gag region are indispensable for high level HIV-1 resistance to protease inhibitors"J.Biol.Chem.. 277. 5952-5961 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mituya H.: "Textbook of AIDS Medicine"Williams & Wilkins. 1064 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa A. et al: "Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells"J.Virol.. 77(6). 3777-3784 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa A. et al: "Replacement of the V3 Region of gp 120 with SDF-1 Preserves the Infectivity of T-Cell Line-Tropic Human Immunodeficiency Virus Type 1"J. Virol. 75(9). 4258-4267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichiyama K. et al: "A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity."Proc. Natl. Acad. Sci. USA. 100(7). 4185-4190 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura Y. et al: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection."Proc. Natl. Acad. Sci. USA. 100(5). 2777-2782 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura T. et al: "Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeficiency virus during highly active antiretroviral therapy"J. Infect. Dis.. 185(1). 53-60 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang FX, et al: "Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type 1-infected patients undergoing highly active antiretroviral therapy"J. Infect. Dis.. 185(5). 608-617 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gatanada H. et al: "Amino acid substitutions in non-cleavage sites of the gag region are indispensable for high level HIV-1 resistance to protease inhibitors"J. Biol. Chem.. 277. 5952-5961 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa T. et al: "Identification of amino acid residues critical for LD78β (a variant of human macrophage inflammatory protein-1 α) binding to CCR5 and inhibition of R5 HIV-1 replication"J. Biol. Chem.. 277. 4649-4655 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa, A: "Replacement of the V3 region of gp120 with SDF-1 preserves the infectivity of T-cell line-tropic human immunodeficiency virus type 1"J. Virol.. 75. 4258-4267 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miura, Y: "Critical contribution of TNF-related apoptosis inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hU-PBL-NOD-SCID mice"J. Exp. Med.. 193. 651-659 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi.Y: "OX40 stimulation by gp34/OX40 ligand enhances productive HIV-1 infection"J. Virol.. 75. 6748-6757 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, K: "Two basic regions of NCp7 are sufficient for conformational conversion of HIV-1 dimerization initiation site from kissing-loop dimer to extended-duplex dimer"J. Biol. Chem.. 276. 31274-31278 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maeda, K: "Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 Infection through their antagonistic effects on CCR5"J. Biol. Chem.. 276. 35194-35200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura, T: "Reconstitution of spontaneous neutralizing antibody response against autologous HiV-1 in chronically infected patients during highly active antiretroviral therapy"J. Infect. Dis.. 185. 53-60 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yonezawa,A: "Replacement of V3 region of gp120 with SDF-1 preserves the infectivity of T-tropic human immunodeficiency virus type 1."J.Virol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Sei,S: "Identification of a key target sequence To block human immunodeficiency virus type 1 replication within the gag-pol tranframe domain."J.Virol. 74. 4621-4633 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Maeda,Y: "Involvement of both V2 and V3 region of CCR5-tropic human immunodeficiency virus type-1 envelope for reduced sensitivity to macrophage inflammatory protein α."J.Virol. 74. 1787-1793 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miura,Y: "Critical contribution of TNF-related apotosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hu-PBL-NOD-SCID mice."J.Exp.Med.. 193. 651-659 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Momoi,Y: "Pertusis toxin enhances human immunodefieicncy virus-1 replication."AIDS Res.Hum.Retroviruses. 16. 373-379 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xu, Y.: "Mearked increase in Anti-HIV activity, as well as inhibitory activity against HIV entry mediated by CXCR4, linked to enhancement of the binding ability of tachyplesin analogs to CXCR4"AIDS Research and Human Retroviruses. 15(5). 419-427 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isaka, Y.: "Small Amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5"Virol. 264. 237-243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liu, H.: "Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression"Proc. Natl. Acad. Sci. USA.. 96. 4581-4585 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Xin, X.: "Enhanced anit-HIV-1 activity of CC-chemokine LD78β a non allelic variant of MIP-1α/LD78α"FEBS Letters. 457(2). 219-222 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, Y.: "Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine induced CD4+ T helper 1 (Th1)- and Th2-type conditions"J Virol. 73. 316-324 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hori T.: "Detection and delineation of CXCR-4(fusin) as an entry and fusion cofactor for T-tropic HIV-1 entry by three different monoclonal antibodies." J Immunol. 160. 180-188 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida H.: "T-tropic human immunodeficiency virus type 1 (HIV-1)-derived V3 loop peptides directly bind to CXCR-4 and inhibit T-tropic HIV-1 infection." J Virol. 72 (2). 9763-9770 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shioda,T.: "Anti-HIV-1 and chemotactic activities of SDF-1α and SDF-1β are abolished by CD26/dipeptidyl peptidase IV mediated cleavage." Proc.Natl.Acad.Sci.USA. 95. 6331-6336 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki Y: "Determinant in human immunodeficiency virus type 1 for efficient replication in cytokine induced CD4+ T helper 1 (Th1)- and Th2-type conditions." J Virol. 73. 316-324 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maeda,Y.: "Altered drug sensitivity and fitness of HIV-1 with pol gene mutations conferring multi-dideoxynucleoside resistance." J.Infect.Dis.177 (5). 1207-1213 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kavlick,M.F.: "Emergence of multi-dideoxynucleoside resistant HIV-1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy." J.Infect.Dis.177 (6). 1506-1513 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2019-02-15  

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