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Phosphorylation of the Epstein-Barr virus BZLF1 immediate-early gene product (ZEBRA)

Research Project

Project/Area Number 06454213
Research Category

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

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionNational Institute of Health

Principal Investigator

SAIRENJI Takashi  National Institute of Health Dept.of Pathol., Head, 感染病理部, 室長 (10117351)

Co-Investigator(Kenkyū-buntansha) MATSUDA Michiyuki  National Institute of Health Dept.of Pathol., Senior Invest., 感染病理部, 主任研究官 (10199812)
KOJIMA Asato  National Institute of Health Dept.of Pathol., Head, 感染病理部, 室長 (30100077)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1995: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1994: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsEpstein-Barr virus (EBV) / BZLF1 / BZLF1 promotor / EBV activation / EBV+T cell line / Second messengers / Chronic fatigue syndrome / Autibody response to human herpesviruses / EBウイルス(EBV) / EBV 前初期遺伝子蛋白(ZEBRA) / ZEBRAのリン酸化
Research Abstract

(1) Regulation of the BZLF1 promoter of Epstein-Barr virus (EBV) by second messengers in anti-immunoglobulin-treated B cells.
The BZLF1 gene promoter (Zp) was activated by crosslinking of cell surface Ig with anti-Ig antibody in B cells.We identified several anti-Ig response elements within Zp.Theatment with calcium ionophore A23187 increased Zp activity.When the calcium ionophore was used in conjunction with TPA,the Zp induction was synergistically enhanced.H7 an inhibitor of PKC,inhibited the anti-Ig inducibility of Zp.Calmodulin antagonists, compound R24571 and trifluoperazine, blocked the Zp activation with anti-Ig.These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calumodulin-dependent protein kinase.Requirement of tyrosine kinase activaion for the anti-Ig-mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin.
(2) Establishment and characterization of the T-cell line, EBT-8 latently i … More nfected with EBV from large granular lymphocyte leukemia.
An EBV genome-positive T-cell line, EBT-8, was established from peripheral blood of a patient with EBV genome-positive large granular lymphocyte leukemia of T-cell origin.Analysis of T-cell receptor gene rearrangement demonstrated similar rearrangement between the fresh leukemic cells and EBT-8 cell line.The cell line has azurophilic granules in its cytoplasm and T-cell surface antigens.The cell line had several chromosomal abnormalities.About five copies of covalently closed circular EBV DNA per cell were detected.EBV-encoded small RNA,EBER1 were demonstrated in all cells.EBNA and LMP1 were demonstrated by immunofluorescence technique.
(3) antibody responses to EBV,human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome (CSF).
To test for an association between CFS and infections with EBV,human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals : (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM ; true chronic IM (CIM) ] ; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) health controls.High EBV antibody titers were demonstrated in most patients.Antibodies to ZEBRA,a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than the controls.These results are consistent with the view that CFS patients may have reactivations of EBV,HHV-6 and HHV-7. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Asada, H. , et al.: "Establishment and characterization of the T-cell line, EBT-8 latently infected with Epstein-Barr virus from large granular lymphocyte leukemia." Leukemia. 8. 1415-1423 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Daibata, M. , et al.: "Regulation of the BZLF1 promoter Epstein-Barr virus by second messengers and anti-immunoglobulin-treated cells." Virology. 198. 446-454 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sairenji, T. et al.: "Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatiguesyndrome" Intervirology. 38. 269-273 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tachibana, Y. , et al.: "A major antigenic region of the integrase (IN) of human immunodeficiency virus type 1 as determined by reactivity of human sera and a monoclonal antibody to IN" Clin. Diag. Lab. Immunol.1. 673-683 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takahashi, H. et al.: "HIV-1 reverse transcriptase : enhancement of activity by interactions with the nucleocapsid p15 protein and cellular topoisomerase I" Proc. Natl. Acad. Sci. USA. 92. 5694-5698 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Gotoh, T. et al.: "Identification of Rap l as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G" Mol. Cell Biol.15. 6746-6753 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sairenji, T., et al.: "Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with Chronic fatigue Syndrome" Intervirology. 38. 269-273 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hara, K., et al.: "Normal activation of p70 S6 Kinase by insulin in cells overexpressing dominant negative 85KD subunit of phosphoincsitide 3-Kinase" Biochem. Biophys. Res. Commun.208. 735-741 (1995)

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

    • Related Report
      1995 Annual Research Report
  • [Publications] Daduang, S. et al.: "Production of monodonal antibodies specific to the carboxyl terminal nagion of the 85KDa subunit of phosphotidyliocsitol 3-kinase" Immunol. Cell Biol.73. 134-139 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Gofoh, T. et al.: "Identification of Rapl as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G" Mol. Cell. Biol.15. 6746-6753 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hasegawa, H. et al.: "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane" Mol. Cell. Biol.16. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Asada,H.,et al.: "Establishment and characterization of the T-cell line,EBT-8 latently infected with Epstein-Barr virus from large granular lymphocyte leukemia." Leukemia. 8. 1415-1423 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Daibata,M.,et al.: "Regulation of the BZLFl promoter Epstein-Barr virus by second messengers and anti-immunoglobul in-treated cells." Virology. 198. 446-454 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tachibana,Y.,et al.: "A major antigenic region of the integrase 〔IN〕 of human immunodeficiency virus type 1 as determined by reactivity of human sera and a monoclonal antibody to IN." Clin.Diag.Lab.Immunol.1. 673-683 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka,S.,et al.: "C3G,a guanine nucleotide-releasing protein expressed ubiquitously,binds to the Src homology 3 domains of CRK and GRB2/ASH proteins" Proc.Natl.Acad.Sci.LISA. 91. 3443-3447 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuda,M.,et al.: "CRK protein bindsto two guanine nucleotide-releasing proteins for the Ras family and modulates neive growth factor-induced activation of Ras in PC12 cells" Mol.Cell.Biol.14. 5495-5499 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takai,S.,et al.: "Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9 & 34.3 by fluorescence in situ hybridization" Hum.Genet.94. 549-550 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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