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Gene therapy of AIDS using the HIV-1 vector carrying the mutated chemokine

Research Project

Project/Area Number 09671126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

OBARU Kenshi  Kumamoto University School of Medicine, Department of Internal Medicine II, Assistant Professor, 医学部・附属病院, 講師 (90281211)

Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsLD78 / chemokines / HIV-1 / CCR5 / gene therapy / CD26 / MIP-1α / CD26 / dipeptidyl peptidase IV
Research Abstract

We found that the human LD78 (MIP-1α) gene family has a wide spectrum of variations including multiplication, deletions, and mutations, and that the LD78 gene family is consisted of at least 10 different subtypes which can be divided into two subfamilies, LD78A and LD78B, based on their N terminal structures. A striking correlation was found between HIV-1 disease progression and the ratio of LD78B and LD78A gene counts: HIV-1 -infected long-term nonprogressors had lower LD78B/LD78A ratios than progressors. An LD78B protein (LD78β) had a greater activity to inhibit the replication of macrophage-tropic HIV-1 in vitro compared to an LD78A protein (LD78α). Mutational analyses of these proteins suggest that the major determinant of functional difference is located at the second amino acid residue of the N terminus. When the effects of CD26 on LD78β, which is cleaved twice by CD26, were examined, single cleavage of LD78β did not affect its CCR5 down-regulation property, while a twice-cleaved LD78b had lesser activity compared to uncleaved LD78b. These results demonstrate the divergence of the LD78 gene family and an importance of the N-terminus of LD78β for its potent anti-HIV-1 function, and may have a relevance in considering human LD78β and its analogs as potential therapeutic agents.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Kenshi Obaru 他7名: "Divergence of the human LD78 (MIP-1α) gene family and the correlation of its constituents with the progression of HIV-1 disease"Journal of Biological Chemistry. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obaru K.: "Chemokine and Chemokine Receptor and HIV infection"Pratical haematology. 8. 65-69 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obaru K. 他1名: "Anti-HIV Drugs and Drug Delivery Systems"Nippon Rinsho - Japanese Journal of Clinical Medicine. 56. 769-775 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morikita T. Maeda Y. Fujii S. Matsushita S. Obaru K. 他1名: "The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitivity to neutralization by soluble CD4 and cellular tropism"AIDS Research & Human Retroviruses. 13. 1291-1299 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Fujii, K.Obaru 他5名: "Characterization of Proviral DNA From an individual With Long-Term Nonprogressive Infection With HIV-1 and Nonrecoverable Virus"Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology. 15. 247-256 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kenshi Obaru, Toshikazu Miyakawa, Sadahiro Tamiya, Ken-ichiro Etoh, KazuhisaYoshimura, Yasuyuki Eda, Oren J. Cohen, and Hiroaki Mitsuya: "Divergence of the human LD78 (MIP-1a) gene family and the correlation of its constituents with the progression of HIV-1diseases"JBC. (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obaru K: "Chemokine and Chemokine Receptor and HIV infection."Practical Haematology. 8. 65-69 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obaru K., Mitsuya H.: "Anti-HIV Drugs and Drug Delivery Systems"Nippon Rinsho - Japanese Journal of Clinical Medicine. 56. 769-775 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morikita T. Maeda Y. Fujii S. Matsushita s. Obaru K. Takatsuki K.: "The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitivity to neutralization by soluble CD4 and cellular tropism."AIDS Research & Human Retroviruses. 13. 1291-1299 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Fujii, K.Obaru, S., Matusita, T.Morikita, H., Higuchi, K., Fujimoto and K., Takatsuki: "Characterization of Proviral DNA From an Individual With Long-Term, Nonprogressive Infection With HIV- 1 and Nonrecoverable Virus."Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology. 15. 247-256 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kenshi Obaru、他1名: "Anti-HIV Drug and Drug Delivery System" Nippon Rinsho. 56. 769-775 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小原健志: "ケモカインおよびケモカインレセプターと病状の進行" Practical Hematology. 8・7. 65-69 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T. Morikita, et al.: "The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitibity of neutralization by soluble CD4 and cellular tropism." AIDS research and human retroviruses. 13. 1291-1299 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii S. et al.: "Characterization of proviral DNA from an individual with long-term, nonprogressive infection with HIV-1 and nonrecoverable virus." J. of AIDS & Human Retrov.15. 247-256 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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