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Basic studies on strategy against HIV

Research Project

Project/Area Number 11557024
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Virology
Research InstitutionThe University of Tokushima

Principal Investigator

ADACHI Akio  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (90127043)

Co-Investigator(Kenkyū-buntansha) UCHIYAMA Tsuneo  The University of Tokushima, School of Medicine, Lecturer, 医学部, 講師 (90151901)
HIMENO Kunisuke  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (50112339)
KOYAMA Hajime  The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (80109074)
AKARI Hirofumi  The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 助手 (20294671)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsHIV / Gag / Env / Vif / Vpr / Nef / Apoptosis / MHC-I / キャプシド
Research Abstract

In this research project, we have obtained the results as summarized below. Our results would contribute much to the understanding of HIV-1 replication and to the development of anti-HIV-1 strategies.
(1) Function of HIV-1 Gag. We have demonstrated the presence of Gag mutants, with defect of uncoating/reverse transcription process in the early phase, that replicate in a cell-dependent manner. This result implies that some cell factor (s) is involved in the process. We also have demonstrated the ability of many of the early Gag mutants to inhibit strongly the replication of wild-type virus.
(2) HIV-1 Env and cellular factor. We have demonstrated the involvement of a host cell factor (s) in the Env incorporation into HIV-1 virions.
(3) Function of HIV-1 Vif. Two HIV-1 Vif mutants, with mutations in the hydrophilic or effector region, have been found to have target cell-dependent replication potentials. These mutants belong to a novel category of the Vif mutants.
(4) Function of HIV-1 Nef. We have found that the region of HIV-1 Nef governing MHC-I down-regulation is proximate in the α helix domain but is dissociated functionally from that determining enhancement of viral infectivity in vitro, virion incorporation of Nef, and CD4 down-regulation. This result suggests that HIV-1 Nef is immunologically important in the infected hosts.
(5) Function of HIV-1 Vpr. Both cell- and virion-associated HIV-1 Vpr have been found to arrest the cell cycle at the G2/M phase and to induce cell apoptosis. No anti-apoptotic activity of HIV-1 Vpr has been noted.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tokunaga,K.: "The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus type 1 Nef protein are ……."Virology. 257. 285-289 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimano,R.: "Inhibition of HIV/SIV replication by dominant negative gag mutants."Virus Genes. 18. 197-201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari,H.: "Pseudotyping HIV-1 by vesicular stomatitis virus G protein does not reduce the cell-dependent requirement of ……."Journal of General Virology. 80. 2945-2949 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari,H.: "Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion ……."Journal of Virology. 74. 2907-2912 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari,H.: "Cell-dependent requirement of human immunodeficiency virus type 1 gp41 cytoplasmic tail for Env incorporation ……."Journal of Virology. 74. 4891-4893 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukumori,T.: "Regulation of cell cycle and apoptosis by HIV-1 Vpr."Microbes and Infection. 2. 1011-1017 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokunaga, K., Ikuta, K., Adachi, A., Matsuda, M., Kurata, T., and Kojima, A.: "The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus type 1 Nef protein are dispensable for producer cell-dependent enhancement of viral entry."Virology. 257. 285-289 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimano, R., Inubushi, R., Oshima, Y., and Adachi, A.: "Inhibition of HIV/SIV replication by dominant negative gag mutants."Virus Genes. 18. 197-201 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari, H., Uchiyama, T., Fukumori, T., Iida, S., Koyama, A.H., and Adachi, A.: "Pseudotyping HIV-1 by vesicular stomatitis virus G protein does not reduce the cell-dependent requirement of Vif for optimal infectivity : functional difference between Vif and Nef."Journal of General Virology. 80. 2945-2949 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari, H., Arold, S., Fukumori, T., Okazaki, T., Strebel, K., and Adachi, A.: "Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation."Journal of Virology. 74. 2907-2912 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari, H., Fukumori, T., and Adachi, A.: "Cell-dependent requirement of human immunodeficiency virus type 1 gp41 cytoplasmic tail for Env incorporation into virions."Journal of Virology. 74. 4891-4893 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukumori, T., Akari, H., Yoshida, A., Fujita, M., Koyama, A.H., Kagawa, S., and Adachi, A.: "Regulation of cell cycle and apoptosis by HIV-1 Vpr."Microbes and Infection. 2. 1011-1017 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akari,H.: "Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated・・・・・."Journal of Virology. 74. 2907-2912 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akari,H.: "Cell-dependent requirement of human immunodeficiency virus type 1 gp41 cytoplasmic tail for Env・・・・・."Journal of Virology. 74. 4891-4893 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koh,K.-B.: "Elimination of HIV-1 plasmid DNA from virus samples obtained from transfection by calcium-phosphate・・・・・."Journal of Virological Methods. 90. 99-102 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukumori,T.: "Regulation of cell cycle and apoptosis by HIV-1 Vpr."Microbes and Infection. 2. 1011-1017 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akari,H.: "Host cell-dependent replication of HIV-1 mutants with deletions in gp41 cytoplasmic tail region is・・・・・."Microbes and Infection. 2. 1019-1023 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koh,K.-B.: "Cell-dependent gag mutants of HIV-1 are crucially defective at the stage of uncoating/reverse・・・・・."Microbes and Infection. 2. 1419-1423 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akari,H.: "Cell-dependent requirement of human immunodeficiency virus type 1 gp41・・・・."Journal of Virology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Nef-induced major histocompatibility complex class I down-regulation is ・・・・."Journal of Virology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isaka,Y.: "Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 ・・・・."Virology. 264. 237-243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Pseudotyping HIV-1 by vesicular stomtitis virus G protein does not reduce the ・・・・."Journal of General Virology. 80. 2945-2949 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akari,H.: "Effects of SIVmac infection on peripheral blood CD4+ CD8+ T lymphocytes in ・・・・."Clinical Immunology. 91. 321-329 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokunaga,K.: "The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus ・・・."Virology. 257. 285-289 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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