Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1990 Jan;9(1):147–152. doi: 10.1002/j.1460-2075.1990.tb08090.x

An Epstein-Barr virus immortalization associated gene segment interferes specifically with the IFN-induced anti-proliferative response in human B-lymphoid cell lines.

P Aman 1, A von Gabain 1
PMCID: PMC551640  PMID: 2153074

Abstract

Immortalization of human B-lymphocytes by Epstein-Barr virus (EBV) is associated with a decreased anti-proliferative response to interferon (IFN). In the present investigation we show that the resistance to the anti-proliferative effect of IFN class I on certain EBV-carrying Burkitt lymphoma cell lines is connected to the presence of the EBNA-2 gene and parts of the EBNA-5 gene of the EBV genome. Transfection of the genomic segment comprising these open reading frames into an IFN-sensitive lymphoma cell line demonstrated that it is sufficient to make cells resistant towards the antiproliferative effect of IFN class I. Expression of the EBNA-2 gene seems to be correlated with the IFN-resistant phenotype. The antiviral function of IFN, as tested by inhibition by vesicular stomatitis virus (VSV) infection, and the IFN-receptor binding are not suppressed. The present results suggest that the neutralization of the anti-proliferative effect of IFN-alpha is involved in the EBV-mediated immortalization of B-cells and that the anti-proliferative action of IFN class I does not necessarily recruit the same mechanism as the antiviral effect.

Full text

PDF
147

Images in this article

149Fig. 4.
on p.149

Selected References

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

  1. Adams A., Lidin B., Strander H., Cantell K. Spontaneous interferon production and Epstein-Barr virus antigen expression in human lymphoid cell lines. J Gen Virol. 1975 Aug;28(2):219–223. doi: 10.1099/0022-1317-28-2-219. [DOI] [PubMed] [Google Scholar]
  2. Adams A., Lindahl T. Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1477–1481. doi: 10.1073/pnas.72.4.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adams A., Strander H., Cantell K. Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon. J Gen Virol. 1975 Aug;28(2):207–217. doi: 10.1099/0022-1317-28-2-207. [DOI] [PubMed] [Google Scholar]
  4. Aguet M., Dembić Z., Merlin G. Molecular cloning and expression of the human interferon-gamma receptor. Cell. 1988 Oct 21;55(2):273–280. doi: 10.1016/0092-8674(88)90050-5. [DOI] [PubMed] [Google Scholar]
  5. Branca A. A., Baglioni C. Evidence that types I and II interferons have different receptors. Nature. 1981 Dec 24;294(5843):768–770. doi: 10.1038/294768a0. [DOI] [PubMed] [Google Scholar]
  6. Delius H., Bornkamm G. W. Heterogeneity of Epstein-Barr virus. III. Comparison of a transforming and a nontransforming virus by partial denaturation mapping of their DNAs. J Virol. 1978 Jul;27(1):81–89. doi: 10.1128/jvi.27.1.81-89.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Diaz M. O., Ziemin S., Le Beau M. M., Pitha P., Smith S. D., Chilcote R. R., Rowley J. D. Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5259–5263. doi: 10.1073/pnas.85.14.5259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dillner J., Kallin B. The Epstein-Barr virus proteins. Adv Cancer Res. 1988;50:95–158. doi: 10.1016/s0065-230x(08)60436-4. [DOI] [PubMed] [Google Scholar]
  9. Einhorn L., Ernberg I. Induction of EBNA precedes the first cellular S-phase after EBV-infection of human lymphocytes. Int J Cancer. 1978 Feb 15;21(2):157–160. doi: 10.1002/ijc.2910210205. [DOI] [PubMed] [Google Scholar]
  10. Finke J., Rowe M., Kallin B., Ernberg I., Rosén A., Dillner J., Klein G. Monoclonal and polyclonal antibodies against Epstein-Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt's lymphoma and lymphoblastoid cell lines. J Virol. 1987 Dec;61(12):3870–3878. doi: 10.1128/jvi.61.12.3870-3878.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gooding L. R., Elmore L. W., Tollefson A. E., Brady H. A., Wold W. S. A 14,700 MW protein from the E3 region of adenovirus inhibits cytolysis by tumor necrosis factor. Cell. 1988 May 6;53(3):341–346. doi: 10.1016/0092-8674(88)90154-7. [DOI] [PubMed] [Google Scholar]
  13. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  14. Hennessy K., Kieff E. A second nuclear protein is encoded by Epstein-Barr virus in latent infection. Science. 1985 Mar 8;227(4691):1238–1240. doi: 10.1126/science.2983420. [DOI] [PubMed] [Google Scholar]
  15. ISAACS A., LINDENMANN J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957 Sep 12;147(927):258–267. doi: 10.1098/rspb.1957.0048. [DOI] [PubMed] [Google Scholar]
  16. Jones M. D., Foster L., Sheedy T., Griffin B. E. The EB virus genome in Daudi Burkitt's lymphoma cells has a deletion similar to that observed in a non-transforming strain (P3HR-1) of the virus. EMBO J. 1984 Apr;3(4):813–821. doi: 10.1002/j.1460-2075.1984.tb01890.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaneko Y., Maseki N., Takasaki N., Sakurai M., Hayashi Y., Nakazawa S., Mori T., Sakurai M., Takeda T., Shikano T. Clinical and hematologic characteristics in acute leukemia with 11q23 translocations. Blood. 1986 Feb;67(2):484–491. [PubMed] [Google Scholar]
  18. Kessler D. S., Pine R., Pfeffer L. M., Levy D. E., Darnell J. E., Jr Cells resistant to interferon are defective in activation of a promoter-binding factor. EMBO J. 1988 Dec 1;7(12):3779–3783. doi: 10.1002/j.1460-2075.1988.tb03262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klein E., Klein G., Nadkarni J. S., Nadkarni J. J., Wigzell H., Clifford P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968 Jul;28(7):1300–1310. [PubMed] [Google Scholar]
  20. Leandersson T., Lundgren E. Cell growth regulation during density inhibition and interferon treatment. Exp Cell Res. 1982 Mar;138(1):167–174. doi: 10.1016/0014-4827(82)90102-1. [DOI] [PubMed] [Google Scholar]
  21. Lotz M., Tsoukas C. D., Fong S., Carson D. A., Vaughan J. H. Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma. Eur J Immunol. 1985 May;15(5):520–525. doi: 10.1002/eji.1830150518. [DOI] [PubMed] [Google Scholar]
  22. Luster A. D., Jhanwar S. C., Chaganti R. S., Kersey J. H., Ravetch J. V. Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. Proc Natl Acad Sci U S A. 1987 May;84(9):2868–2871. doi: 10.1073/pnas.84.9.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matsuyama M., Sairenji T., Yonemura K., Hinuma Y. Interferon production potentials of various human lymphoblastoid cell lines. Microbiol Immunol. 1982;26(12):1149–1158. doi: 10.1111/j.1348-0421.1982.tb00264.x. [DOI] [PubMed] [Google Scholar]
  24. Menezes J., Leibold W., Klein G. Biological differences between Epstein-Barr virus (EBV) strains with regard to lymphocyte transforming ability, superinfection and antigen induction. Exp Cell Res. 1975 May;92(2):478–484. doi: 10.1016/0014-4827(75)90404-8. [DOI] [PubMed] [Google Scholar]
  25. Miller G., Robinson J., Heston L., Lipman M. Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection, and interference. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4006–4010. doi: 10.1073/pnas.71.10.4006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mogensen K. E., Bandu M. T., Vignaux F., Aguet M., Gressner I. Binding of 125I-labelled human alpha interferon to human lymphoid cells. Int J Cancer. 1981 Nov 15;28(5):575–582. doi: 10.1002/ijc.2910280508. [DOI] [PubMed] [Google Scholar]
  27. Nilsson K., Sundström C. Establishment and characteristics of two unique cell lines from patients with lymphosarcoma. Int J Cancer. 1974 Jun 15;13(6):808–823. doi: 10.1002/ijc.2910130609. [DOI] [PubMed] [Google Scholar]
  28. Nonoyama M., Pagano J. S. Detection of Epstein-Barr viral genome in nonproductive cells. Nat New Biol. 1971 Sep 22;233(38):103–106. doi: 10.1038/newbio233103a0. [DOI] [PubMed] [Google Scholar]
  29. PULVERTAFT J. V. A STUDY OF MALIGNANT TUMOURS IN NIGERIA BY SHORT-TERM TISSUE CULTURE. J Clin Pathol. 1965 May;18:261–273. doi: 10.1136/jcp.18.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  31. Pfitzner A. J., Tsai E. C., Strominger J. L., Speck S. H. Isolation and characterization of cDNA clones corresponding to transcripts from the BamHI H and F regions of the Epstein-Barr virus genome. J Virol. 1987 Sep;61(9):2902–2909. doi: 10.1128/jvi.61.9.2902-2909.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Reich N., Pine R., Levy D., Darnell J. E., Jr Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products. J Virol. 1988 Jan;62(1):114–119. doi: 10.1128/jvi.62.1.114-119.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ricksten A., Svensson C., Welinder C., Rymo L. Identification of sequences in Epstein-Barr virus DNA required for the expression of the second Epstein-Barr virus-determined nuclear antigen in COS-1 cells. J Gen Virol. 1987 Sep;68(Pt 9):2407–2418. doi: 10.1099/0022-1317-68-9-2407. [DOI] [PubMed] [Google Scholar]
  35. Robinson J., Smith D. Infection of human B lymphocytes with high multiplicities of Epstein-Barr virus: kinetics of EBNA expression, cellular DNA synthesis, and mitosis. Virology. 1981 Mar;109(2):336–343. doi: 10.1016/0042-6822(81)90504-3. [DOI] [PubMed] [Google Scholar]
  36. Rymo L., Klein G., Ricksten A. Expression of a second Epstein-Barr virus-determined nuclear antigen in mouse cells after gene transfer with a cloned fragment of the viral genome. Proc Natl Acad Sci U S A. 1985 May;82(10):3435–3439. doi: 10.1073/pnas.82.10.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Steinitz M., Bakács T., Klein G. Interaction of the B95-8 and P3HR-1 substrains of Epstein-Barr virus (EBV) with peripheral human lymphocytes. Int J Cancer. 1978 Sep 15;22(3):251–257. doi: 10.1002/ijc.2910220306. [DOI] [PubMed] [Google Scholar]
  39. Strander H. Interferon treatment of human neoplasia. Adv Cancer Res. 1986;46:1–265. [PubMed] [Google Scholar]
  40. Strander H., Mogensen K. E., Cantell K. Production of human lymphoblastoid interferon. J Clin Microbiol. 1975 Jan;1(1):116–117. doi: 10.1128/jcm.1.1.116-117.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Thorley-Lawson D. A., Chess L., Strominger J. L. Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. J Exp Med. 1977 Aug 1;146(2):495–508. doi: 10.1084/jem.146.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Thorley-Lawson D. A. The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon. J Immunol. 1981 Mar;126(3):829–833. [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES