Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jun 1;88(11):4766–4770. doi: 10.1073/pnas.88.11.4766

Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells.

H Herbst 1, F Dallenbach 1, M Hummel 1, G Niedobitek 1, S Pileri 1, N Müller-Lantzsch 1, H Stein 1
PMCID: PMC51747  PMID: 1647016

Abstract

Cryostat sections from lymph nodes of 47 Hodgkin disease patients were examined by immunohistology for the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP), nuclear antigen 2, and late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in Hodgkin and Reed-Sternberg cells in 18 patients (38%); EBV nuclear antigen 2 and gp350/250 immunoreactivity was absent in all instances. Thirty-two of 47 (68%) cases contained EBV-specific DNA sequences as detected by PCR, all LMP-positive cases being in this category. Our results confirm previous studies establishing the presence of EBV genomes in Hodgkin and Reed-Sternberg cells by demonstrating expression of an EBV-encoded protein in the tumor-cell population. The finding of LMP expression in the absence of EBV nuclear antigen 2 suggests a pattern of EBV gene expression different from that of B-lymphoblastoid cell lines and Burkitt lymphoma, whereas this finding shows similarities with that seen in undifferentiated nasopharyngeal carcinoma. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiological role of EBV in many cases of Hodgkin disease.

Full text

PDF
4767

Images in this article

4767Image
on p.4767
4769Image
on p.4769
4769Image
on p.4769

Selected References

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

  1. Anagnostopoulos I., Herbst H., Niedobitek G., Stein H. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood. 1989 Aug 1;74(2):810–816. [PubMed] [Google Scholar]
  2. Boos H., Berger R., Kuklik-Roos C., Iftner T., Mueller-Lantzsch N. Enhancement of Epstein-Barr virus membrane protein (LMP) expression by serum, TPA, or n-butyrate in latently infected Raji cells. Virology. 1987 Jul;159(1):161–165. doi: 10.1016/0042-6822(87)90360-6. [DOI] [PubMed] [Google Scholar]
  3. Boos H., Stoehr M., Sauter M., Mueller-Lantzsch N. Flow cytometric analysis of Epstein-Barr virus (EBV) latent membrane protein expression in EBV-infected Raji cells. J Gen Virol. 1990 Aug;71(Pt 8):1811–1815. doi: 10.1099/0022-1317-71-8-1811. [DOI] [PubMed] [Google Scholar]
  4. Cleary M. L., Sklar J. Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas. Lancet. 1984 Sep 1;2(8401):489–493. doi: 10.1016/s0140-6736(84)92566-2. [DOI] [PubMed] [Google Scholar]
  5. Dawson C. W., Rickinson A. B., Young L. S. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990 Apr 19;344(6268):777–780. doi: 10.1038/344777a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fåhraeus R., Rymo L., Rhim J. S., Klein G. Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature. 1990 May 31;345(6274):447–449. doi: 10.1038/345447a0. [DOI] [PubMed] [Google Scholar]
  8. Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
  9. Gutensohn N., Cole P. Epidemiology of Hodgkin's disease. Semin Oncol. 1980 Jun;7(2):92–102. [PubMed] [Google Scholar]
  10. Harabuchi Y., Yamanaka N., Kataura A., Imai S., Kinoshita T., Mizuno F., Osato T. Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet. 1990 Jan 20;335(8682):128–130. doi: 10.1016/0140-6736(90)90002-m. [DOI] [PubMed] [Google Scholar]
  11. Hennessy K., Fennewald S., Hummel M., Cole T., Kieff E. A membrane protein encoded by Epstein-Barr virus in latent growth-transforming infection. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7207–7211. doi: 10.1073/pnas.81.22.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herbst H., Niedobitek G., Kneba M., Hummel M., Finn T., Anagnostopoulos I., Bergholz M., Krieger G., Stein H. High incidence of Epstein-Barr virus genomes in Hodgkin's disease. Am J Pathol. 1990 Jul;137(1):13–18. [PMC free article] [PubMed] [Google Scholar]
  13. Hillinger S. M., Herzig G. P. Impaired cell-mediated immunity in Hodgkin's disease mediated by suppressor lymphocytes and monocytes. J Clin Invest. 1978 Jun;61(6):1620–1627. doi: 10.1172/JCI109082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knecht H., Sahli R., Shaw P., Meyer C., Bachmann E., Odermatt B. F., Bachmann F. Detection of Epstein-Barr virus DNA by polymerase chain reaction in lymph node biopsies from patients with angioimmunoblastic lymphadenopathy. Br J Haematol. 1990 Aug;75(4):610–614. doi: 10.1111/j.1365-2141.1990.tb07807.x. [DOI] [PubMed] [Google Scholar]
  15. Liebowitz D., Kopan R., Fuchs E., Sample J., Kieff E. An Epstein-Barr virus transforming protein associates with vimentin in lymphocytes. Mol Cell Biol. 1987 Jul;7(7):2299–2308. doi: 10.1128/mcb.7.7.2299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mueller-Lantzsch N., Lenoir G. M., Sauter M., Takaki K., Béchet J. M., Kuklik-Roos C., Wunderlich D., Bornkamm G. W. Identification of the coding region for a second Epstein-Barr virus nuclear antigen (EBNA 2) by transfection of cloned DNA fragments. EMBO J. 1985 Jul;4(7):1805–1811. doi: 10.1002/j.1460-2075.1985.tb03854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mueller N., Evans A., Harris N. L., Comstock G. W., Jellum E., Magnus K., Orentreich N., Polk B. F., Vogelman J. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med. 1989 Mar 16;320(11):689–695. doi: 10.1056/NEJM198903163201103. [DOI] [PubMed] [Google Scholar]
  18. Reedman B. M., Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. doi: 10.1002/ijc.2910110302. [DOI] [PubMed] [Google Scholar]
  19. Rogers R. P., Woisetschlaeger M., Speck S. H. Alternative splicing dictates translational start in Epstein-Barr virus transcripts. EMBO J. 1990 Jul;9(7):2273–2277. doi: 10.1002/j.1460-2075.1990.tb07398.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  21. Stein H., Gatter K., Asbahr H., Mason D. Y. Use of freeze-dried paraffin-embedded sections for immunohistologic staining with monoclonal antibodies. Lab Invest. 1985 Jun;52(6):676–683. [PubMed] [Google Scholar]
  22. 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]
  23. Wang D., Liebowitz D., Wang F., Gregory C., Rickinson A., Larson R., Springer T., Kieff E. Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity. J Virol. 1988 Nov;62(11):4173–4184. doi: 10.1128/jvi.62.11.4173-4184.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wang F., Gregory C., Sample C., Rowe M., Liebowitz D., Murray R., Rickinson A., Kieff E. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol. 1990 May;64(5):2309–2318. doi: 10.1128/jvi.64.5.2309-2318.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med. 1989 Feb 23;320(8):502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  26. Wilson J. B., Weinberg W., Johnson R., Yuspa S., Levine A. J. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell. 1990 Jun 29;61(7):1315–1327. doi: 10.1016/0092-8674(90)90695-b. [DOI] [PubMed] [Google Scholar]
  27. Young L. S., Dawson C. W., Clark D., Rupani H., Busson P., Tursz T., Johnson A., Rickinson A. B. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988 May;69(Pt 5):1051–1065. doi: 10.1099/0022-1317-69-5-1051. [DOI] [PubMed] [Google Scholar]
  28. zur Hausen H., Schulte-Holthausen H., Klein G., Henle W., Henle G., Clifford P., Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970 Dec 12;228(5276):1056–1058. doi: 10.1038/2281056a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES