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.
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References and Recommended Reading
Epstein MA, Achong BG, Barr YM: Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964, 1:702–703.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Bibeau F, Brousset P, Knecht H, et al.: Epstein-Barr virus replication in Hodgkin’s disease. Bull Cancer 1994, 81:114–188.
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.
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.
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.
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.
Chen W-G, Chen Y-Y, Kamel OW, et al.:p53 mutations in Hodgkin’s disease. Lab Invest 1996, 75:519–527.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Liebowitz D: Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients. N Engl J Med 1998, 338:1413–1421.
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.
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.
Heslop HE, Rooney CM: Adoptive cellular immunotherapy for EBV lymphoproliferative diseases. Immunol Rev 1997, 157:217–222.
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.
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.
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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
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DOI: https://doi.org/10.1007/s11912-000-0094-9