Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1995 Sep;48(9):845–848. doi: 10.1136/jcp.48.9.845

Down-regulation of Epstein-Barr virus nuclear antigen 1 in Reed-Sternberg cells of Hodgkin's disease.

G Khan 1, M A Naase 1
PMCID: PMC502874  PMID: 7490319

Abstract

AIMS--To demonstrate Epstein-Barr virus (EBV) encoded nuclear antigen 1 (EBNA-1) gene expression in EBV associated disorders using a new monoclonal antibody (1H4-1) on routinely processed tissues. METHODS--The pressure cooker antigen retrieval method was used for the immunohistochemical demonstration of EBNA-1 gene expression in formalin fixed, EBV positive tissues from Hodgkin's disease, infectious mononucleosis, HIV associated non-Hodgkin's lymphomas, post-transplant lymphomas, and undifferentiated nasopharyngeal carcinoma (NPC). EBV encoded EBNA-2, latent membrane protein 1 (LMP-1) and BZLF-1 gene expression was also examined using commercially available monoclonal antibodies. RESULTS--Of the 34 EBER in situ hybridisation positive cases of Hodgkin's disease examined, none expressed EBNA-1 in the Reed-Sternberg cells. These cells were nevertheless strongly LMP-1 positive in all cases. Strong EBNA-1 staining was seen in all cases of EBER positive HIV associated non-Hodgkin's lymphoma (five of five), nasopharyngeal carcinoma (five of five), infectious mononucleosis (three of three), and post-transplant lymphoma (one of one). These cases also expressed LMP-1, EBNA-2 and BZLF-1, but at differing levels. CONCLUSION--The pressure cooker antigen retrieval procedure is a sensitive and reliable adjunct to immunohistochemistry, especially with antibodies which are otherwise ineffective on routinely processed tissues. The EBNA-1 gene is not expressed at detectable levels in the malignant cells of Hodgkin's disease, but is consistently expressed in other EBV associated disorders. This finding has important implications for the role of EBNA-1 in the biology of EBV.

Full text

PDF
845

Images in this article

846Image
on p.846
847Image
on p.847

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambinder R. F., Mann R. B. Detection and characterization of Epstein-Barr virus in clinical specimens. Am J Pathol. 1994 Aug;145(2):239–252. [PMC free article] [PubMed] [Google Scholar]
  2. Deacon E. M., Pallesen G., Niedobitek G., Crocker J., Brooks L., Rickinson A. B., Young L. S. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med. 1993 Feb 1;177(2):339–349. doi: 10.1084/jem.177.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Falk K., Ernberg I., Sakthivel R., Davis J., Christensson B., Luka J., Okano M., Grierson H. L., Klein G., Purtilo D. T. Expression of Epstein-Barr virus-encoded proteins and B-cell markers in fatal infectious mononucleosis. Int J Cancer. 1990 Dec 15;46(6):976–984. doi: 10.1002/ijc.2910460605. [DOI] [PubMed] [Google Scholar]
  4. Fåhraeus R., Fu H. L., Ernberg I., Finke J., Rowe M., Klein G., Falk K., Nilsson E., Yadav M., Busson P. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 1988 Sep 15;42(3):329–338. doi: 10.1002/ijc.2910420305. [DOI] [PubMed] [Google Scholar]
  5. Gilligan K., Rajadurai P., Resnick L., Raab-Traub N. Epstein-Barr virus small nuclear RNAs are not expressed in permissively infected cells in AIDS-associated leukoplakia. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8790–8794. doi: 10.1073/pnas.87.22.8790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gratama J. W., Zutter M. M., Minarovits J., Oosterveer M. A., Thomas E. D., Klein G., Ernberg I. Expression of Epstein-Barr virus-encoded growth-transformation-associated proteins in lymphoproliferations of bone-marrow transplant recipients. Int J Cancer. 1991 Jan 21;47(2):188–192. doi: 10.1002/ijc.2910470205. [DOI] [PubMed] [Google Scholar]
  7. Grässer F. A., Murray P. G., Kremmer E., Klein K., Remberger K., Feiden W., Reynolds G., Niedobitek G., Young L. S., Mueller-Lantzsch N. 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 Dec 1;84(11):3792–3798. [PubMed] [Google Scholar]
  8. Henle G., Henle W., Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan;59(1):94–101. doi: 10.1073/pnas.59.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jones C. H., Hayward S. D., Rawlins D. R. Interaction of the lymphocyte-derived Epstein-Barr virus nuclear antigen EBNA-1 with its DNA-binding sites. J Virol. 1989 Jan;63(1):101–110. doi: 10.1128/jvi.63.1.101-110.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Khan G., Coates P. J., Gupta R. K., Kangro H. O., Slavin G. Presence of Epstein-Barr virus in Hodgkin's disease is not exclusive to Reed-Sternberg cells. Am J Pathol. 1992 Apr;140(4):757–762. [PMC free article] [PubMed] [Google Scholar]
  11. Khan G., Coates P. J., Kangro H. O., Slavin G. Epstein Barr virus (EBV) encoded small RNAs: targets for detection by in situ hybridisation with oligonucleotide probes. J Clin Pathol. 1992 Jul;45(7):616–620. doi: 10.1136/jcp.45.7.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Khan G., Coates P. J. The role of Epstein-Barr virus in the pathogenesis of Hodgkin's disease. J Pathol. 1994 Nov;174(3):141–149. doi: 10.1002/path.1711740302. [DOI] [PubMed] [Google Scholar]
  13. Khan G., Norton A. J., Slavin G. Epstein-Barr virus in Hodgkin disease. Relation to age and subtype. Cancer. 1993 May 15;71(10):3124–3129. doi: 10.1002/1097-0142(19930515)71:10<3124::aid-cncr2820711038>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  14. Knecht H., Brousset P., Bachmann E., Sandvej K., Odermatt B. F. Latent membrane protein 1: a key oncogene in EBV-related carcinogenesis? Acta Haematol. 1993;90(4):167–171. doi: 10.1159/000204451. [DOI] [PubMed] [Google Scholar]
  15. Norton A. J., Jordan S., Yeomans P. Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues. J Pathol. 1994 Aug;173(4):371–379. doi: 10.1002/path.1711730413. [DOI] [PubMed] [Google Scholar]
  16. Pallesen G., Hamilton-Dutoit S. J., Zhou X. The association of Epstein-Barr virus (EBV) with T cell lymphoproliferations and Hodgkin's disease: two new developments in the EBV field. Adv Cancer Res. 1993;62:179–239. doi: 10.1016/s0065-230x(08)60319-x. [DOI] [PubMed] [Google Scholar]
  17. Rickinson A. B., Murray R. J., Brooks J., Griffin H., Moss D. J., Masucci M. G. T cell recognition of Epstein-Barr virus associated lymphomas. Cancer Surv. 1992;13:53–80. [PubMed] [Google Scholar]
  18. Rickinson A. B., Young L. S., Rowe M. Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J Virol. 1987 May;61(5):1310–1317. doi: 10.1128/jvi.61.5.1310-1317.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roth G., Curiel T., Lacy J. Epstein-Barr viral nuclear antigen 1 antisense oligodeoxynucleotide inhibits proliferation of Epstein-Barr virus-immortalized B cells. Blood. 1994 Jul 15;84(2):582–587. [PubMed] [Google Scholar]
  20. Snudden D. K., Hearing J., Smith P. R., Grässer F. A., Griffin B. E. EBNA-1, the major nuclear antigen of Epstein-Barr virus, resembles 'RGG' RNA binding proteins. EMBO J. 1994 Oct 17;13(20):4840–4847. doi: 10.1002/j.1460-2075.1994.tb06810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Thomas J. A., Hotchin N. A., Allday M. J., Amlot P., Rose M., Yacoub M., Crawford D. H. Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation. 1990 May;49(5):944–953. doi: 10.1097/00007890-199005000-00022. [DOI] [PubMed] [Google Scholar]
  22. Tierney R. J., Steven N., Young L. S., Rickinson A. B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol. 1994 Nov;68(11):7374–7385. doi: 10.1128/jvi.68.11.7374-7385.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tomkinson B., Robertson E., Kieff E. Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. J Virol. 1993 Apr;67(4):2014–2025. doi: 10.1128/jvi.67.4.2014-2025.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wang D., Liebowitz D., Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985 Dec;43(3 Pt 2):831–840. doi: 10.1016/0092-8674(85)90256-9. [DOI] [PubMed] [Google Scholar]
  25. Wang F., Gregory C. D., Rowe M., Rickinson A. B., Wang D., Birkenbach M., Kikutani H., Kishimoto T., Kieff E. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. Proc Natl Acad Sci U S A. 1987 May;84(10):3452–3456. doi: 10.1073/pnas.84.10.3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wilson J. B., Levine A. J. The oncogenic potential of Epstein-Barr virus nuclear antigen 1 in transgenic mice. Curr Top Microbiol Immunol. 1992;182:375–384. doi: 10.1007/978-3-642-77633-5_48. [DOI] [PubMed] [Google Scholar]
  27. Yates J., Warren N., Reisman D., Sugden B. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806–3810. doi: 10.1073/pnas.81.12.3806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES