1995 Fiscal Year Final Research Report Summary
Phosphorylation of the Epstein-Barr virus BZLF1 immediate-early gene product (ZEBRA)
| Project/Area Number |
06454213
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Health |
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Principal Investigator |
SAIRENJI Takashi National Institute of Health Dept.of Pathol., Head, 感染病理部, 室長 (10117351)
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| 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)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Epstein-Barr virus (EBV) / BZLF1 / BZLF1 promotor / EBV activation / EBV+T cell line / Second messengers / Chronic fatigue syndrome / Autibody response to human herpesviruses |
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| 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
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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
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