Skip to main content

Advertisement

Log in

Epstein-Barr virus and hodgkin’s disease

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Approximately 40% to 50% of cases of Hodgkin’s disease occurring in Western populations are associated with the Epstein-Barr virus (EBV). In these cases, EBV is found in the neoplastic elements, the Reed-Sternberg and Hodgkin’s cells. EBV is probably not present in all cases, but neither have any other viruses been found in the cases that are EBV-negative. EBV may play a role in the pathogenesis of Hodgkin’s disease by the activation of anti-apoptotic factors in a premalignant germinal center B-lymphocyte. Regardless of their role in etiology or pathogenesis, EBV-latent antigens may represent a target for possible immune therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Epstein MA, Achong BG, Barr YM: Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964, 1:702–703.

    Article  PubMed  CAS  Google Scholar 

  2. Mueller N, Evans A, Harris NL, et al.: Hodgkin’s disease and Epstein-Barr virus: altered antibody pattern before diagnosis. N Engl J Med 1989, 320:689–692.

    Article  PubMed  CAS  Google Scholar 

  3. Sample J, Young L, Martin B, et al.: Epstein-Barr virus types 1 and 2 differ in the EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol 1990, 64:4084–4092.

    PubMed  CAS  Google Scholar 

  4. Ambinder RF, Weiss LM: Association of Epstein-Barr virus with Hodgkin’s disease. In Hodgkin’s Disease. Edited by Mauch PM, Armitage JO, Diehl V, et al. Philadelphia: Lippincott Williams & Wilkins; 1999:79–98. This chapter provides a thorough review of the association of EBV with Hodgkin’s disease. It also provides a good background on the biology of EBV.

    Google Scholar 

  5. Weiss LM, Mohaved LA, Warnke RA, Sklar J: Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 1989, 320:502–506.

    Article  PubMed  CAS  Google Scholar 

  6. Weiss LM, Chen Y-Y, Liu X-F, Shibata D: Epstein-Barr virus and Hodgkin’s disease: a correlative in situ hybridization and polymerase chain reaction study. Am J Pathol 1991, 139:1259–1265.

    PubMed  CAS  Google Scholar 

  7. Herbst H, Steinbrecher E, Niedobitek G, et al.: Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin’s disease. Blood 1992, 80:484–491.

    PubMed  CAS  Google Scholar 

  8. Vasef MA, Kamel OW, Chen Y-Y, et al.: Detection of Epstein-Barr virus in multiple sites involved by Hodgkin’s disease. Am J Pathol 1995, 147:1408–1415.

    PubMed  CAS  Google Scholar 

  9. Weiss LM, Strickler JG, Warnke RA, et al.: Epstein-Barr viral DNA in tissues of Hodgkin’s disease. Am J Pathol 1987, 129:86–91.

    PubMed  CAS  Google Scholar 

  10. Gulley ML, Eagan PA, Quintanilla-Martinez L, et al.: Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin’s disease: association with mixed cellularity subtype and Hispanic American ethnicity. Blood 1994, 83:1595–1602.

    PubMed  CAS  Google Scholar 

  11. Grasser FA, Murray PG, Kremmer E, et al.: Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin’s disease. Blood 1994, 84:3792–3798.

    PubMed  CAS  Google Scholar 

  12. Hummel M, Anagnostopoulos I, Dallenbach F, et al.: EBV infection patterns in Hodgkin’s disease and normal lymphoid tissue: expression and cellular localization of EBV gene products. Br J Haematol 1992, 82:689–694.

    PubMed  CAS  Google Scholar 

  13. Deacon EM, Pallesen G, Niedobitek G, et al.: Epstein-Barr virus and Hodgkin’s disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med 1993, 177:339–349.

    Article  PubMed  CAS  Google Scholar 

  14. Bibeau F, Brousset P, Knecht H, et al.: Epstein-Barr virus replication in Hodgkin’s disease. Bull Cancer 1994, 81:114–188.

    PubMed  CAS  Google Scholar 

  15. Pallesen G, Sandvej K, Hamilton-Dutoit SJ, et al.: Activation of Epstein-Barr virus replication in Hodgkin’s and Reed-Sternberg cells. Blood 1991, 78:1162–1165.

    PubMed  CAS  Google Scholar 

  16. Gallagher A, Armstrong AA, MacKenzie J, et al.: Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin’s disease. Int J Cancer 1999, 84:442–448.

    Article  PubMed  CAS  Google Scholar 

  17. Glaser SL, Lin RJ, Stewart S, et al.: Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. Int J Cancer 1997, 70:375–382.

    Article  PubMed  CAS  Google Scholar 

  18. Khalidi H, Lones MA, Zhou Y, et al.: Detection of Epstein-Bar virus in the L&H cells of nodular lymphocytic predominance Hodgkin’s disease: report of a case documented by immunohistochemical, in situ hybridization, and polymerase chain reaction methods. Am J Clin Pathol 1997, 108:687–692.

    PubMed  CAS  Google Scholar 

  19. Chen W-G, Chen Y-Y, Kamel OW, et al.:p53 mutations in Hodgkin’s disease. Lab Invest 1996, 75:519–527.

    PubMed  CAS  Google Scholar 

  20. Murray PG, Constandinou CM, Crocker J, et al.: Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin’s disease. Blood 1998, 92:2477–2483.

    PubMed  CAS  Google Scholar 

  21. Jarrett RF, Gallagher A, Jones DB, et al.: Detection of Epstein-Barr virus genomes in Hodgkin’s disease: relation to age. J Clin Pathol 1991, 44:844–848.

    PubMed  CAS  Google Scholar 

  22. Chang KL, Albujar PF, Chen Y-Y, et al.: High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin’s disease occurring in Peru. Blood 1993, 81:496–502.

    PubMed  CAS  Google Scholar 

  23. Ambinder RF, Browning PJ, Lorenzana I, et al.: Epstein-Barr virus and childhood Hodgkin’s disease in Honduras and the United States. Blood 1993, 81:462–467.

    PubMed  CAS  Google Scholar 

  24. Uccini S, Monardo F, Stoppacciaro A, et al.: High frequency of Epstein-Barr virus genome detection in Hodgkin’s disease of HIV-positive patients. Int J Cancer 1990, 46:581–585.

    Article  PubMed  CAS  Google Scholar 

  25. Herndier BG, Sanchez HC, Chang KL, et al.: High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin’s disease. Am J Pathol 1993, 142:1073–1079.

    PubMed  CAS  Google Scholar 

  26. Sleckman BG, Mauch PM, Ambinder RF, et al.: Epstein-Barr virus in Hodgkin’s disease: correlation of risk factors and disease characteristics with molecular evidence of viral infection. Cancer Epidemiol Biomarkers Prev 1998, 7:1117–1121.

    PubMed  CAS  Google Scholar 

  27. Levine PH, Pallesen G, Ebbesen P, et al.: Evaluation of Epstein-Barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin’s disease. Int J Cancer 1994, 59:48–50.

    Article  PubMed  CAS  Google Scholar 

  28. Enblad G, Sandvej K, Lennette E, et al.: Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin’s disease. Int J Cancer 1997, 72:394–397.

    Article  PubMed  CAS  Google Scholar 

  29. O’Grady J, Stewart S, Elton RA, Krajewski AS: Epstein-Barr virus in Hodgkin’s disease and site of origin of tumour. Lancet 1994, 343:265–266.

    Article  PubMed  CAS  Google Scholar 

  30. Murray PG, Billingham LJ, Hassan HT, et al.: Effect of Epstein-Barr virus infection on response to chemotherapy and survival in Hodgkin’s disease. Blood 1999, 94:442–447.

    PubMed  CAS  Google Scholar 

  31. Knecht H, Bachmann E, Brousset P, et al.: Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin’s disease and identical to those observed in nasopharyngeal carcinoma. Blood 1993, 82:2937–2942.

    PubMed  CAS  Google Scholar 

  32. Chen M-L, Tsai C-N, Liang C-L, et al.: Cloning and characterization of the latent membrane protein (LMP) of a specific Epstein-Barr virus variant derived from the nasopharyngeal carcinoma in the Taiwanese population. Oncogene 1992, 7:2131–2140.

    PubMed  CAS  Google Scholar 

  33. Hayashi K, Chen W-G, Chen Y-Y, et al.: Deletion of the latent membrane protein 1 in United States and Brazilian Hodgkin’s disease and reactive lymphoid tissue: high frequency of a 30-base pair deletion. Hum Pathol 1997, 28:1408–1414.

    Article  PubMed  CAS  Google Scholar 

  34. Chang KL, Chen YY, Chen WG, et al.: EBNA-1 gene sequences in Brazilian and American patients with Hodgkin’s disease. Blood 1999, 94:244–250.

    PubMed  CAS  Google Scholar 

  35. Chu PG, Chang KL, Chen Y-Y, et al.: EBV nuclear antigen (EBNA)-4 mutation in EBV-associated Hodgkin’s disease and gastric carcinoma in different ethnic groups. Am J Pathol 1999, 155:941–949.

    PubMed  CAS  Google Scholar 

  36. Shimizu N, Tanabetochikura A, Kuroiwa Y, Takada K: Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt’s lymphoma (BL) line: Akata-malignant phenotypes of BL cells are dependent on EBV. J Virol 1994, 68:6069–6073.

    PubMed  CAS  Google Scholar 

  37. Jox A, Rohen C, Belge G, et al.: Integration of Epstein-Barr virus in Burkitt’s lymphoma cells leads to a region of enhanced chromosome instability. Ann Oncol 1997, 8:5131–5135.

    Article  Google Scholar 

  38. Razzouk BI, Srinivas S, Sample CE, et al.: Epstein-Barr virus DNA recombination and loss in sporadic Burkitt’s lymphoma. J Infect Dis 1996, 173:529–535.

    PubMed  CAS  Google Scholar 

  39. Jarrett RF, MacKenzie J: Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin’s disease. Semin Hematol 1999, 36:260–269. This article provides an excellent review of the association of EBV with Hodgkin’s disease. It offers a particularly good discussion on the epidemiology of Hodgkin’s disease and the search for other viruses.

    PubMed  CAS  Google Scholar 

  40. Evans AS, Gutensohn NM: A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin’s disease and their siblings. Int J Cancer 1984, 34:149–157.

    Article  PubMed  CAS  Google Scholar 

  41. Armstrong AA, Shield L, Gallagher A, Jarrett RF: Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin’s disease. Br J Cancer 1998, 77:1045–1047.

    PubMed  CAS  Google Scholar 

  42. Momose H, Jaffe ES, Shin SS, et al.: Chronic lymphocytic leukemia/small lymphocytic lymphoma with Reed-Sternberglike cells and possible transformation to Hodgkin’s disease: mediation by Epstein-Barr virus. Am J Surg Pathol 1992, 16:859–867.

    Article  PubMed  CAS  Google Scholar 

  43. Kuppers R, Rajewsky K: The origin of Hodgkin and Reed-Sternberg cells in Hodgkin’s disease. Ann Rev Immunol 1998, 16:471–493. This review provides a thorough discussion on the origin of Hodgkin’s and Reed-Sternberg cells and the pathogenesis of Hodgkin’s disease.

    Article  CAS  Google Scholar 

  44. Bargou RC, Emmerich F, Krappmann D, et al.: Constitutive nuclear factor-kB-RelA activation is required for proliferation and survival of Hodgkin’s disease tumor cells. J Clin Invest 1997, 100:2961–2969.

    Article  PubMed  CAS  Google Scholar 

  45. Liebowitz D: Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients. N Engl J Med 1998, 338:1413–1421.

    Article  PubMed  CAS  Google Scholar 

  46. Durkop H, Foss HD, Demel G, et al.: Tumor necrosis factor receptor-associated factor 1 is overexpressed in Reed-Sternberg cells of Hodgkin’s disease and Epstein-Barr virus-transformed lymphoid cells. Blood 1999, 93:617–623. This paper provides evidence for a direct role for EBV in the pathogenesis of Hodgkin’s disease.

    PubMed  CAS  Google Scholar 

  47. Lee SY, Park CG, Choi Y: T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptorassociated factors. J Exp Med 1996, 183:669–674.

    Article  PubMed  CAS  Google Scholar 

  48. Heslop HE, Rooney CM: Adoptive cellular immunotherapy for EBV lymphoproliferative diseases. Immunol Rev 1997, 157:217–222.

    Article  PubMed  CAS  Google Scholar 

  49. Sing AP, Ambinder RF, Hong DJ, et al.: Isolation of Epstein-Barr virus-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin’s disease. Blood 1997, 89:1978–1986.

    PubMed  CAS  Google Scholar 

  50. Roskrow MA, Suzuki N, Gan Y, et al.: Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin’s disease. Blood 1998, 91:2925–2934. This article describes the use of cytotoxic T lymphomas as potential adjuvant therapy for the treatment of patients with EBV-positive relapsed Hodgkin’s disease.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weiss, L.M. Epstein-Barr virus and hodgkin’s disease. Curr Oncol Rep 2, 199–204 (2000). https://doi.org/10.1007/s11912-000-0094-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-000-0094-9

Keywords

Navigation