Expression of bcl-2 protein and transcription of the Epstein-Barr virus bcl-2 homologue BHRF-1 in Hodgkin's disease: implications for different pathogenic mechanisms

Epstein–Barr virus (EBV) is associated with several malignancies. Specific EBV gene variants, e.g. the BamHI f configuration, a C-terminal region 30 bp deletion in the latent membrane protein-1 (LMP1) gene (del-LMP) and the loss of an XhoI site in LMP1 (XhoI-loss), are found in Chinese cases of nasopharyngeal carcinoma (NPC), suggesting that EBV sequence variation may be involved in oncogenesis. In order to understand better the epidemiology of these EBV variants, they were studied in virus isolates from EBV-positive Chinese cases of Hodgkin’s disease (HD; n=71) and donor throat washings from healthy Chinese. Sequencing was performed of 15 representative EBV isolates, including the first analysis of the LMP1 promoter in Asian wild-type EBV isolates. The following observations were made. (i) Three EBV LMP1 variants were identified, designated Chinese groups (CG) 1–3. In both EBV-associated HD and in healthy Chinese, CG1-like viruses showing del-LMP1 and XhoI-loss were predominant. (ii) CG1viruses were distinct from European and African variants, suggesting that this profile is useful for epidemiological studies. (iii) Specific patterns of mutations were present in the LMP1 promoter in both CG1 and CG2. (iv) The BamHI f variant was not found in Chinese HD, in contrast to Chinese NPC and European HD. This study confirms that EBV isolates in Chinese HD and other tumours differ from those reported in Western cases. However, this reflects the predominant virus strain present in the healthy Chinese population, suggesting that these are geographically restricted polymorphisms rather than tumour-specific strains.

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Evaluation of epstein-barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease

International Journal of Cancer ◽

10.1002/ijc.2910590111 ◽

1994 ◽

Vol 59 (1) ◽

pp. 48-50 ◽

Cited By ~ 22

Author(s):

Paul H. Levine ◽

Gorm Pallesen ◽

Peter Ebbesen ◽

Nancy Harris ◽

Alfred S. Evans ◽

...

Keyword(s):

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Virus Antibody ◽

Barr Virus ◽

Epstein Barr

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High Epstein-Barr virus serum load and elevated titers of anti-ZEBRA antibodies in patients with EBV-harboring tumor cells of Hodgkin's disease

Journal of Medical Virology ◽

10.1002/(sici)1096-9071(199904)57:4<383::aid-jmv10>3.0.co;2-3 ◽

1999 ◽

Vol 57 (4) ◽

pp. 383-389 ◽

Cited By ~ 46

Author(s):

Emmanuel Drouet ◽

Pierre Brousset ◽

Fouad Fares ◽

Josette Icart ◽

C�cile Verniol ◽

...

Keyword(s):

Tumor Cells ◽

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Barr Virus ◽

Epstein Barr

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Epstein-Barr virus and hodgkin’s disease

International Journal of Clinical & Laboratory Research ◽

10.1007/bf02592274 ◽

1993 ◽

Vol 23 (1-4) ◽

pp. 13-16 ◽

Cited By ~ 18

Author(s):

Hermann Herbst ◽

Gerald Niedobitek

Keyword(s):

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Barr Virus ◽

Epstein Barr

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Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes for the Treatment of Patients With EBV-Positive Relapsed Hodgkin's Disease

Blood ◽

10.1182/blood.v91.8.2925.2925_2925_2934 ◽

1998 ◽

Vol 91 (8) ◽

pp. 2925-2934 ◽

Cited By ~ 215

Author(s):

Marie A. Roskrow ◽

Nobuhiro Suzuki ◽

Yan-jun Gan ◽

John W. Sixbey ◽

Catherine Y.C. Ng ◽

...

Keyword(s):

Tumor Cells ◽

Cytotoxic T Lymphocytes ◽

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Barr Virus ◽

Specific Ctls ◽

Epstein Barr ◽

Relapsed Disease

Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) is effective prophylaxis and treatment of EBV-positive immunoblastic lymphoma in immunocompromised patients. In 50% of patients with Hodgkin's disease, the tumor cells are EBV antigen-positive and may therefore also be suitable targets for treatment with virus-specific CTLs. However, Hodgkin's disease may produce several inhibitory effects on immune induction and effector function in vivo, which may preclude the generation or effector function of CTLs reactive against EBV viral proteins, including those expressed by the tumor cells. We have investigated whether EBV-specific CTLs could be generated ex vivo from 13 patients with Hodgkin's disease: nine with active relapsed disease and four who were in clinical remission after a first or subsequent relapse. CTL lines were successfully generated from nine of 13 patients (five active disease, four remission). Although these lines had an abnormal pattern of expansion comparable to EBV-specific CTLs generated from normal donors, their phenotype was normal except for reduced expression of the zeta chain of the T-cell receptor (TCR). Their cytotoxicity was also compared to EBV-specific lines generated from normal donors and included activity against LMP2a, one of the three weakly immunogenic viral antigens expressed by Hodgkin's tumor cells. To assess the activity of the CTLs in vivo, they were gene-marked and infused into three patients with multiply relapsed disease. The CTLs persisted for more than 13 weeks postinfusion and retained their potent antiviral effects in vivo, thereby enhancing the patient immune response to EBV. This approach may therefore have value in the treatment of EBV-positive Hodgkin's disease.

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