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エイズの病態と制御に関する基礎研究 柱1.HIVの複製機構

Research Project

Project/Area Number 07277104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokushima

Principal Investigator

足立 昭夫  徳島大学, 医学部, 教授 (90127043)

Co-Investigator(Kenkyū-buntansha) 中村 義一  東京大学, 医科学研究所, 助教授 (40114590)
水落 次男  東海大学, 工学部, 教授 (90133149)
小島 朝人  国立感染症研究所, 感染病理部, 室長 (研究職) (30100077)
木戸 博  徳島大学, 分子酵素学研究センター, 教授 (50144978)
岡本 尚  名古屋市立大学, 医学部, 教授 (40146600)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥111,000,000 (Direct Cost: ¥111,000,000)
Fiscal Year 1997: ¥41,100,000 (Direct Cost: ¥41,100,000)
Fiscal Year 1996: ¥33,400,000 (Direct Cost: ¥33,400,000)
Fiscal Year 1995: ¥36,500,000 (Direct Cost: ¥36,500,000)
KeywordsHIV / Gag / NF-kB / プロテアーゼ / Nef / 人工糖脂質被覆リポソーム / フレームシフト / Vpr / Vif / アポトーシス / HIV複製 / アクセサリー蛋白質 / Gag蛋白質 / 人工糖脂質
Research Abstract

足立はHIV-1のGagの機能領域を確定した。GagはHIV-1複製の初期及び後期に重要な役割を果たしている。MAとCAは初期・後期に、NCとp6はそれぞれ初期と後期に必須である。変異体を用いて解析したところ、CA変異体の多くが非常に強力に野性株の複製を阻害することがわかり、遺伝子治療の標的遺伝子となり得ることが明らかとなった。岡本は、HIVプロウイルス活性化因子であるNF-kBを活性化するNF-kB kinaseをヒト末梢血Tリンパ球分画より精製し、種々のリン酸化酵素阻害剤の効果を調べた。H8,H9,HA1077がNF-kB kinase活性を阻害した。さらに、HA1077はTNFによる持続感染細胞からのHIV誘導をも阻害した。木戸は、HIVgp120のV3領域と相互作用するtryptase TL2には6種のアイソマ-があることを見出した。C型アイソマ-はプロテインキナーゼ FRAPと特異的に複合体を形成し、FRAPの自己リン酸化を促進し、T細胞の活性化に関与している。木戸は、またPlasminと類似したセリン性プロテアーゼがHIV外膜蛋白質の成熟に関与することを明らかにした。小島は足立との共同研究で、HIV-1のNefが細胞内侵入過程と逆転写過程の2つの作用点で複製を調節していることを示した。水落は、特定糖鎖を導入した人工糖脂質で被覆したリポソームがフロイントの完全アジュバントよりも強い遅延型アレルギー反応誘導能を持つこと、また、CD8陽性のCTLを強く誘導できることを示した。この人工糖脂質を用いてサルにおけるSIVの感染防御及び発症阻止試験を実施する予定である。中村はフレームシフトを標的とするエイズ医薬品の開発に取組んでいる。

Report

(3 results)
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kawamura,M.: "Functional Domain Mapping of HIV-1 Gag proteins" Biochemical and Biophysical Research Communications. 241. 317-320 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Furuta,R.A.: "HIV-1 capsid mutants inhibit the replication of wild-type virus at both early and late infection phases" FEBS Letters. 415. 231-234 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Simano,R.: "Inhibition of HIV replication by capsid mutant C6b" Biochemical and Biophysical Research Communications. 242. 313-316 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakano,T.: "Clonal selection of HIV type 1 variants associated with resistance to foscarnet in vitro : confirmation by molecular・・・・・." AIDS Research and Human Retroviruses. 13. 563-573 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chiba,J.: "Generation of neutralizing antibody to the reverse trans-criptase of human immunodeficiency virus type 1 by ・・・・・." Journal of Immunological Methods. 207. 53-60 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moriwaki,T.: "Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin β-subunit by disruption of ・・・・・." Glycoconjugate Journal. 14. 225-229 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kido,H.: "Cellular Proteinases and Viral Infection(B.M.Dunn ed.)" Academic Press,San Diego, (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,Y.: "Soluble Nef antigen of HIV-1 is cytotoxic for human CD4+ T cells" FEBS Letters. 393. 93-96 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujii,Y.: "Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells" FEBS Letters. 393. 105-108 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujii,Y.: "In vitro cytocidal effects of HIV-1 Nef of unprimed human CD4+ T cells without MHC-restriction" Journal of General Virology. 77. 2943-2951 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakano,T.: "Clonal selection of foscarnet-resistant HIV-1 variants in vitro" AIDS Research and Human Retroviruses. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kido,H.: "Cellular proteases involved in the pathogenicity of human immunodeficiency and influenza viruses" Advances in Experimental Medicine and Biology. 389. 233-240 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsushita,M.: "A novel human serum lectin with collagen-and fibrinogen-like domains which functions as an opsonin" Journal of Biological Chemistry. 271. 2448-2454 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakuragi,J.: "Generation and characterization of a host cell-dependent gag gene mutant of human immunodeficiency virus type 1" Virology. 212. 251-254 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakai,H.: "Function of human immunodeficiency virus type 1 Vpu protein in various cell types" Journal of General Virology. 76. 2717-2722 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yang,J.P.: "Inhibition of the DNA-binding activity of NF-kB by gold compounds in vitro" FEBS Letters. 361. 89-96 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimizu,N.: "Detection of typtase TL2 and CD26 antigen in brain-derived cells non-permissive to T-cell line-tropic HIV-1" FEBS Letters. 358. 48-52 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takahashi,H.: "HIV-1 reverse transcriptase : Enhancement of activity by interactions with the nucleocapsid p15 protein and ・・・・・" Proc.Natl.Acad.Sci.,USA.92. 5694-5698 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsushita,M.: "A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin" Journal of Biological Chemistry. 271. 2448-2454 (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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