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Studies on Pathogenesis of Chronic Active Epstein-Barr Virus Infection

Research Project

Project/Area Number 14570750
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKochi University

Principal Investigator

WAKIGUCHI Hiroshi  Kochi University, Dpt of Pediatrics, Professor, 医学部, 教授 (10116519)

Co-Investigator(Kenkyū-buntansha) IMAI Shosuke  Kochi University, Dpt of Mol.Microbiol.Infect., Professor, 医学部, 教授 (60232592)
MAEDA Akihiko  Kochi University, Dpt of Pediatrics, Instructor, 医学部, 助手 (50335931)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsChronic Active Epstein-Barr Virus Infection / T / NK-cell proliferation / EBV latent gene / T, NK細胞増殖
Research Abstract

Chronic active Epstein-Barr virus(EBV) infection(CAEBV) is a lethal T-or NK-lymphoproliferative disease often occurring in children. This study aimed to clarify the unknown pathogenesis of CAEBV, from which the establishment of a novel remedial strategy against the disease will also benefit.
The approach undertaken in this study is to seek for a latent EBV gene(s) resposible for uncontrolled T-or NK-cell-proliferation, which can functionally replace the role of entire EBV genome in the virus-positive T-or NK-cell lines derived from patients with CAEBV. We prepared improved self-inactivating retroviral vectors(SIN-RVs) that can express individual EBV latent genes, e.g., EBNA1, LMP1, LMP2A, BARF0, A73, RPMS1 and EBERs. Also, we successfully constructed an EBNA1 mutant, and incorporated it into the fiber-replaced adenovirus type 5 vector(Adv5/35f-DNE1). Adv5/35f-DNE1 proved that the EBNA1 mutant efficiently eradicates EBV episomes from infected cells and concomitantly impedes the virus-dependent aggressive growth phenotypes of EBV-positive T-or NK-cell lines, thereby indicating that our EBNA1 mutant can act as a dominant-negative(dn) EBNA1.
Based on the above data, we have just entered the final aspect of experiments to identify the EBV latent gene(s) essential to T-or NK-cell-proliferation. In parallel, we are invetigating now into whether our dnEBNA1 will provide an additional therapeutic molecule specifically targeting EBV-associated malignancies, by some ways including animal experiments.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kanamori M, et al.: "Epstein-Barr virus nuclear antigen leader protein induces expression of thymus and activation-regulated chemokine in B cells."J Virol. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa J, et al.: "Up-regulation of truncated basic hair keratin 1(hHb1-ΔN) in carcinoma cells by Epstein-Barr virus (EBV)."Int J Cancer. 101. 597-602 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto K, et al.: "Eosinophil degranulation during pregnancy and after delivery by cesarean section."Int Arch Allergy Immunol. 131. 34-39 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato A, et al.: "Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006."BMC Immunology. 4. 8 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura T, et al.: "Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease."Bone Marrow Transplantation. 31. 105-111 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura H, et al.: "Prognostic factors for chronic active Epstein-Barr virus infection."J.Infect.Dis.. 187. 527-533 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanamori M, et al.: "Epstein-Barr virus nuclear antigen leader protein induces expression of thymus and activation-regulated chemokine in B cells."J Virol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa J, et al.: "Up-regulation of truncated basic hair keratin 1(hHb1-ΔN) in carcinoma cells by Epstein-Barr virus(EBV)."Int J Cancer. 107(4). 597-602 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto K, et al.: "Eosinophil degranulation during pregnancy and after delivery by cesarean section."Int Arch Allergy Immunol. 131. 34-39 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato A, et al.: "Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006."BMC Immunology. 4. 8 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura T, et al.: "Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease."Bone Marrow Transplantation. 31. 105-111 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura H, et al.: "Prognostic factors for chronic active Epstein-Barr virus infection."J.Infect.Dis.. 187. 527-533 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto K, et al.: "Eosinophil degranulation during pregnancy and after delivery by cesaren section"Int Arch Allergy Immunol. 131. 34-39 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato A, et al.: "Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006"BMC Immunology. 4. 8 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okamura T, et al.: "Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease"Bone Marrow Transplantation. 31. 105-111 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuzaki S, et al.: "Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophageφMR11"J.Infect.Dis.. 187. 613-624 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura H, et al.: "Prognostic factors for chronic active Epstein-Barr virus infection"J.Infect.Dis.. 187. 527-533 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakiguchi H.: "Overview of Epstein-Barr virus-associated diseases in Japan"Critical Reviews in Oncology/Hematology. 44. 193-202 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura H, Wakiguchi H, et al.: "Prognostic Factors for Chronic Active Epstein-Barr Virus Infection"The Journal of Infectious Diseases. 187. 527-533 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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