Skip to main content
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
. 1987 May;84(10):3452–3456. doi: 10.1073/pnas.84.10.3452

Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23.

F Wang, C D Gregory, M Rowe, A B Rickinson, D Wang, M Birkenbach, H Kikutani, T Kishimoto, E Kieff
PMCID: PMC304889  PMID: 3033649

Abstract

Epstein-Barr virus (EBV) infection of EBV-negative Burkitt lymphoma (BL) cells induces some changes similar to those seen in normal B lymphocytes that have been growth transformed by EBV. The role of individual EBV genes in this process was evaluated by introducing each of the viral genes that are normally expressed in EBV growth-transformed and latently infected lymphoblasts into an EBV-negative BL cell line, using recombinant retrovirus-mediated transfer. Clones of cells were derived that stably express the EBV nuclear antigen 1 (EBNA-1), EBNA-2, EBNA-3, EBNA-leader protein, or EBV latent membrane protein (LMP). These were compared with control clones infected with the retrovirus vector. All 10 clones converted to EBNA-2 expression differed from control clones or clones expressing other EBV proteins by growth in tight clumps and by markedly increased expression of one particular surface marker of B-cell activation, CD23. Other activation antigens were unaffected by EBNA-2 expression, as were markers already expressed on the parent BL cell line, including BL markers (cALLA and BLA), proliferation markers (transferrin receptor and BK19.9), and cell adhesion-related molecules (LFA-1 and LFA-3). Increased CD23 expression in cells expressing EBNA-2 was apparent from monoclonal anti-CD23 antibody binding to the cell surface, from immunoprecipitation of the 45-kDa and 90-kDa CD23 proteins with monoclonal antibody, and from RNA blots probed with labeled CD23 DNA. The results indicate that EBNA-2 is a specific direct or indirect trans-activator of CD23. This establishes a link between an EBV gene and cell gene expression. Since CD23 has been implicated in the transduction of B-cell growth signals, its specific induction by EBNA-2 could be important in EBV induction of B-lymphocyte transformation.

Full text

PDF
3452

Images in this article

Selected References

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

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Bodescot M., Brison O., Perricaudet M. An Epstein-Barr virus transcription unit is at least 84 kilobases long. Nucleic Acids Res. 1986 Mar 25;14(6):2611–2620. doi: 10.1093/nar/14.6.2611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Dambaugh T., Wang F., Hennessy K., Woodland E., Rickinson A., Kieff E. Expression of the Epstein-Barr virus nuclear protein 2 in rodent cells. J Virol. 1986 Aug;59(2):453–462. doi: 10.1128/jvi.59.2.453-462.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gerber P., Hoyer B. H. Induction of cellular DNA synthesis in human leukocytes by Epstein-Barr virus. Nature. 1971 May 7;231(5297):46–47. doi: 10.1038/231046a0. [DOI] [PubMed] [Google Scholar]
  7. Gordon J., Rowe M., Walker L., Guy G. Ligation of the CD23,p45 (BLAST-2,EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes. Eur J Immunol. 1986 Sep;16(9):1075–1080. doi: 10.1002/eji.1830160908. [DOI] [PubMed] [Google Scholar]
  8. Gordon J., Webb A. J., Walker L., Guy G. R., Rowe M. Evidence for an association between CD23 and the receptor for a low molecular weight B cell growth factor. Eur J Immunol. 1986 Dec;16(12):1627–1630. doi: 10.1002/eji.1830161225. [DOI] [PubMed] [Google Scholar]
  9. Greene W. C., Leonard W. J., Wano Y., Svetlik P. B., Peffer N. J., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. Trans-activator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression. Science. 1986 May 16;232(4752):877–880. doi: 10.1126/science.3010456. [DOI] [PubMed] [Google Scholar]
  10. Henle W., Diehl V., Kohn G., Zur Hausen H., Henle G. Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science. 1967 Sep 1;157(3792):1064–1065. doi: 10.1126/science.157.3792.1064. [DOI] [PubMed] [Google Scholar]
  11. Hennessy K., Wang F., Bushman E. W., Kieff E. Definitive identification of a member of the Epstein-Barr virus nuclear protein 3 family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5693–5697. doi: 10.1073/pnas.83.15.5693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kikutani H., Inui S., Sato R., Barsumian E. L., Owaki H., Yamasaki K., Kaisho T., Uchibayashi N., Hardy R. R., Hirano T. Molecular structure of human lymphocyte receptor for immunoglobulin E. Cell. 1986 Dec 5;47(5):657–665. doi: 10.1016/0092-8674(86)90508-8. [DOI] [PubMed] [Google Scholar]
  13. Kikutani H., Suemura M., Owaki H., Nakamura H., Sato R., Yamasaki K., Barsumian E. L., Hardy R. R., Kishimoto T. Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. J Exp Med. 1986 Nov 1;164(5):1455–1469. doi: 10.1084/jem.164.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mann K. P., Staunton D., Thorley-Lawson D. A. Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells. J Virol. 1985 Sep;55(3):710–720. doi: 10.1128/jvi.55.3.710-720.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mehta S. R., Conrad D., Sandler R., Morgan J., Montagna R., Maizel A. L. Purification of human B cell growth factor. J Immunol. 1985 Nov;135(5):3298–3302. [PubMed] [Google Scholar]
  16. Miller A. D., Jolly D. J., Friedmann T., Verma I. M. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4709–4713. doi: 10.1073/pnas.80.15.4709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miller A. D., Law M. F., Verma I. M. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol. 1985 Mar;5(3):431–437. doi: 10.1128/mcb.5.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Naharro G., Robbins K. C., Reddy E. P. Gene product of v-fgr onc: hybrid protein containing a portion of actin and a tyrosine-specific protein kinase. Science. 1984 Jan 6;223(4631):63–66. doi: 10.1126/science.6318314. [DOI] [PubMed] [Google Scholar]
  19. Nilsson K., Klein G. Phenotypic and cytogenetic characteristics of human B-lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma. Adv Cancer Res. 1982;37:319–380. doi: 10.1016/s0065-230x(08)60886-6. [DOI] [PubMed] [Google Scholar]
  20. Peterson L. H., Conrad D. H. Fine specificity, structure, and proteolytic susceptibility of the human lymphocyte receptor for IgE. J Immunol. 1985 Oct;135(4):2654–2660. [PubMed] [Google Scholar]
  21. Pope J. H., Horne M. K., Scott W. Transformation of foetal human keukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer. 1968 Nov 15;3(6):857–866. doi: 10.1002/ijc.2910030619. [DOI] [PubMed] [Google Scholar]
  22. Rosén A., Gergely P., Jondal M., Klein G., Britton S. Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytes in vitro. Nature. 1977 May 5;267(5606):52–54. doi: 10.1038/267052a0. [DOI] [PubMed] [Google Scholar]
  23. Rowe M., Hildreth J. E., Rickinson A. B., Epstein M. A. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity. Int J Cancer. 1982 Apr 15;29(4):373–381. doi: 10.1002/ijc.2910290403. [DOI] [PubMed] [Google Scholar]
  24. Rowe M., Rooney C. M., Edwards C. F., Lenoir G. M., Rickinson A. B. Epstein-Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma. Int J Cancer. 1986 Mar 15;37(3):367–373. doi: 10.1002/ijc.2910370307. [DOI] [PubMed] [Google Scholar]
  25. Rowe M., Rooney C. M., Rickinson A. B., Lenoir G. M., Rupani H., Moss D. J., Stein H., Epstein M. A. Distinctions between endemic and sporadic forms of Epstein-Barr virus-positive Burkitt's lymphoma. Int J Cancer. 1985 Apr 15;35(4):435–441. doi: 10.1002/ijc.2910350404. [DOI] [PubMed] [Google Scholar]
  26. Sample J., Hummel M., Braun D., Birkenbach M., Kieff E. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096–5100. doi: 10.1073/pnas.83.14.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Skare J., Farley J., Strominger J. L., Fresen K. O., Cho M. S., zur Hausen H. Transformation by Epstein-Barr virus requires DNA sequences in the region of BamHI fragments Y and H. J Virol. 1985 Aug;55(2):286–297. doi: 10.1128/jvi.55.2.286-297.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Steinitz M., Klein G. Further studies on the differences in serum dependence in EBV negative lymphoma lines and their in vitro EBV converted, virus-genome carrying sublines. Eur J Cancer. 1977 Nov;13(11):1269–1275. doi: 10.1016/0014-2964(77)90035-4. [DOI] [PubMed] [Google Scholar]
  30. Sugden B., Metzenberg S. Characterization of an antigen whose cell surface expression is induced by infection with Epstein-Barr virus. J Virol. 1983 Jun;46(3):800–807. doi: 10.1128/jvi.46.3.800-807.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  33. Volsky D. J., Gross T., Sinangil F., Kuszynski C., Bartzatt R., Dambaugh T., Kieff E. Expression of Epstein-Barr virus (EBV) DNA and cloned DNA fragments in human lymphocytes following Sendai virus envelope-mediated gene transfer. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5926–5930. doi: 10.1073/pnas.81.19.5926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Walker L., Guy G., Brown G., Rowe M., Milner A. E., Gordon J. Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle. Immunology. 1986 Aug;58(4):583–589. [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Wang F., Petti L., Braun D., Seung S., Kieff E. A bicistronic Epstein-Barr virus mRNA encodes two nuclear proteins in latently infected, growth-transformed lymphocytes. J Virol. 1987 Apr;61(4):945–954. doi: 10.1128/jvi.61.4.945-954.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams D. A., Lemischka I. R., Nathan D. G., Mulligan R. C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature. 1984 Aug 9;310(5977):476–480. doi: 10.1038/310476a0. [DOI] [PubMed] [Google Scholar]
  38. Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [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