• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

エイズ制圧へ向けての基礎研究 柱2 HIVの生物学

Research Project

Project/Area Number 04269102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTokyo Medical and Dental University

Principal Investigator

山本 直樹  東京医科歯科大学, 医学部, 教授 (00094053)

Co-Investigator(Kenkyū-buntansha) 星野 洪郎  群馬大学, 医学部, 教授 (00107434)
生田 和良  北海道大学, 免疫科学研究所, 教授 (60127181)
原田 信志  熊本大学, 医学部, 教授 (60173085)
Project Period (FY) 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥105,400,000 (Direct Cost: ¥105,400,000)
Fiscal Year 1994: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1993: ¥39,700,000 (Direct Cost: ¥39,700,000)
Fiscal Year 1992: ¥28,700,000 (Direct Cost: ¥28,700,000)
Keywordsエイズ / HIV / 潜伏感染 / 持続感染 / 薬剤耐性 / トロピズム / 宿主因子 / 変異 / 脳由来細胞 / 中和 / 変異株
Research Abstract

HIVと宿主の相互作用を主としてウイルス学的に研究し、各班員がそれぞれ以下の結果を得た。
HIV-1が感染していながらその発現はほとんどない単球・マクロファージ系の細胞株(J22HL-60、U1)を用いて、種々の刺激によるウイルスの誘導を行い、その機序解明を試みた。その結果、LPS誘導ではCD14、ジアシルグリセロールがまた、コレラ毒素と百日咳毒素でG蛋白が関与していることがわかった。またマイコプラスマからユニークなホスホコリン含有グリセロ糖脂質を見い出した。(山本)
プロテアーゼ阻害剤(RPI312)を使用し耐性HIVを得た。この耐性HIVは、pol遺伝子の2082がA→Gと変異していた。184→Vのアミノ酸変化が起こり、そのため薬剤耐性となったと考えられた。またマイコプラブマ由来の逆転写酵素阻害物質を同定した。(原田)
リンパ球およびマクロファージ系細胞におけるHIVの潜伏・持続感染成立機序は極めて多様であったが、特にMT-4細胞ではウイルスのアクセサリー遺伝子(vif,vpr)の変異(nonsense変異やmisalignment欠失など)に相関すること、またこの変異はnefの存在下でのみ起こることが明らかになった。(生田)
CD4を発現するようにしたグリオーマ細胞を用い、新しい変異株の分離を試みた。GUN-1株より数種の変異株を分離した。また、分離した8つのHIV-1株を用い、新たにGUN-4およびGUN-7の変異株を分離し、V3領域のアミノ酸配列をDNAの塩基配列から推定し野性株と比較した。(星野)

Report

(3 results)
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Chowdhury IH: "cAMP stimulates human immunodeficiency virus(HIV-1)from latently infected cells of monocyte-macrophage lineage:Synergism with TNF-α" Virology. 194. 345-349 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chowdhury IH: "Pertussis toxin inhibits induction of human immunodeficiency virus type 1 infected monocytes" Virology. 203. 378-383 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mastuda K: "Glycosphingolipid compositionsof human T-lymphotropic virus type 1(HTLV-1)and human immunodeficiency virus(HIV)-infected cell lines" Biochim Biophys Acta. 1168. 123-9 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuda K: "Occurrence of a novel glycolipid containing phosphocholine in HTLV-1-infected cells" Glycoconjugate J. 10. 340 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuda K: "Characterization of a novel phosphocoline-containing glycoglycerolipid from M.fermentans" J.Biol Chem. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishida Y: "Synthesis and absolute configuration of 6-0-phosphocholine-α-D-glucopyranosyl glycerolipid isolated from HTLV-1-infected cell lines" Tetrahedron Lett. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Chowdhury IH: "Mycoplasma stimulated HIV-1 expression from acutely-and dormantly-infected promonocyte/monoblastoid cell line" Arch Virol. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] EL-Farrash MA: "Generation and characterization of a human immunodeficiency virus type1(HIV-1)mutant resistant to an HIV-1 protease inhibitor" J Virol. 68. 233-239 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishino Y: "Presistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus" J Gen Virol. 75. 2241-2251 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakaya R: "Nonsense mutations in the vpr gene of HIV-1 carrier-derived peripheral blood mononuclear cells" FEBS Lett. 354. 17-22 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kimura T: "Amplification of superoxide anion generation in phagocytic cells by HIV-1 infection" FEBS Lett. 326. 232-236 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kameoka M: "Superoxide enhances the spread of HIV-1 infection by cell-to-cell transmission" FEBS Lett. 331. 182-186 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujii Y: "Evidence for the role of human immunodeficiency virus type 1 Nef protein as a growth inhibitor to CD4+ T lymphocytes and for the blocking of the Nef function by anti-Nef antibodies" Vaccine. 11. 837-847 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujii Y: "Expression of human immunodeficiency virus type 1 Nef antigen on the surface of acutely and persistently infected human T cells" Vaccine. 11. 1240-1246 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Otake: "The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells" J Immunol. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimizu SN: "Isolation and cheracterization of humman immunodeficiency virus type 1 variants infectious to brain-derived cells:detection of common point mutations in the V3 region of the env gene of the variants" J Virol. 239. 6130-6135 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 山本ほか: "cAMP stimulates human immunodeficiency virus(HIV-1) from latently infected cells of monocyte-macrophage lineage:synergism with TNF-α." Virology. 194. 345-349 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山本ほか: "Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus(HIV)-infected cell lines." Biochem.Biophys.Acta. 1168. 123-129 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山本ほか: "Defensins inhibit HIV replication in vitro." AIDS. 7. 1129-1129 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 原田ほか: "Modulation of host cell nuclear proteins that bind to HIV-1 trans-activation-responsive element RNA by phorbol ester." Virology. 192. 696-700 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 原田ほか: "In vitro modification of human immunodeficiency virus type 1 (HIV-1) infectivity by the U937 cells." Microbiol.Immunol.37. 349-357 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 原田ほか: "Analysis of 3' terminals of human immunodeficiency virus Type 1 transcripts in persistently infected cells." Virus Gene. 7. 241-253 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山本ほか: "Anti-human immunodeficiency virus activity of a novel synthetic peptide.T22([Tyr-5,12,Lys-7]polyphemusin II):a possible inhibitor of virus-cell fusion." Antimicrob.Agents Chemother.,. 36. 1249-1255 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山本ほか: "Increased production of human immunodeficiency virus (HIV) in HIV-induced syncytia formation:An efficient infection process." Virus Gene,. 6. 63-78 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山本ほか: "Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy." Ann.Neurol.,. 31. 39-45 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 原田ほか: "Analysis of 3'terminal of human immunodeficiency virus type 1 transcripts in persistemtly infected cells." Virus Gene,.

    • Related Report
      1992 Annual Research Report
  • [Publications] 原田ほか: "Coexistence of fusion receptors for human T-cell leukemia virus type-I (HTLV-I) and human immunodeficiency virus type-1 (HIV-1) on MOLT-4 cell." Microbiol.Immunol.,. 35. 729-740 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 原田ほか: "Inhibition of human immunodeficiency virus replication in a human T cell line by antisense RNA expression in the cell." Virus Gene,. 5. 189-202 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 生田ほか: "Monoclonal antibodies to a CD4 peptide derivative which includes the region corresponding to an immunoglobulin CDR3:evidence of the involvement of pre-CDR3-related region in HIV-1 and host cell interaction." Molecular Immology,.

    • Related Report
      1992 Annual Research Report
  • [Publications] 生田ほか: "Characterization of a unique scrambled peptide derived from the CD4 CDR3-related region which shows substantial activity for blocking HIV-1 infection." Vaccine,.

    • Related Report
      1992 Annual Research Report
  • [Publications] 生田ほか: "Alterd cell tropism and cytopathicity of feline immunodeficiency viruses in two different feline CD4-positive,CD8-negative cell lines." J.Virol.,. 66. 3893-3898 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 星野ほか: "Six strains of human immunodeficiency virus type-1 isolated in Japan and their molecular phylogeny." J.Mol.Evol.,.

    • Related Report
      1992 Annual Research Report
  • [Publications] 星野ほか: "Inhibition of heat inactivation of reverse transcriptase of human immunodeficiency virus type 1 by seropositive sera." Jpn.J.Cancer Res.,. 83. 594-600 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 星野ほか: "Host range mutant of human immunodeficiency virus type 1:modification of cell tropism by a single point mutation at the neutralization eqitope in the gene." J.Virol.,. 65. 1710-1718 (1991)

    • Related Report
      1992 Annual Research Report

URL: 

Published: 1992-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi