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PMID: 1406670 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The EBNA2-related resistance towards alpha interferon (IFN-alpha) in Burkitt's lymphoma cells effects induction of IFN-induced genes but not the activation of transcription factor ISGF-3.

Molecular and cellular biology ·Vol. 12 ·No. 11 ·1992-11-00 ·Pages 4930-6

Kanda K, Decker T, Aman P, Wahlström M, von Gabain A, Kallin B

Abstract

Transfection of a plasmid encoding the Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene confers resistance to the antiproliferative effect of alpha interferon (IFN-alpha) in EBV-negative U968 cells (P. Aman and A. von Gabain, EMBO J. 9:147-152, 1990). We studied the expression of IFN-stimulated genes (ISGs) in two pairs of Burkitt's lymphoma cell lines, differing in the expression of the putative immortalizing gene of EBV, EBNA2. In EBNA2-expressing cells, the induction of four ISGs by IFN-alpha was strongly reduced or, in some cases, abolished. Chloramphenicol acetyltransferase reporter gene constructs containing different IFN-stimulated response elements were transfected into EBNA2-negative and EBNA2-positive cells. Induction of chloramphenicol acetyltransferase activity by IFN was impaired in EBNA2-positive cells. Also, a reporter gene construct driven by an IFN-gamma-sensitive promoter element was affected. However, as revealed by gel shift assays, EBNA2-positive and EBNA2-negative cells exhibited a nearly identical pattern of IFN-stimulated response element-binding proteins. Most important, activation of the factor ISGF-3, which previously has been shown to be required and sufficient for transcriptional activation of IFN-induced genes, was not inhibited in IFN-resistant cells expressing EBNA2. The mechanism of the EBNA2-related IFN resistance seems to be distinct both from the resistance mediated by hepatitis virus and adenovirus gene products and from the IFN resistance in Daudi cell variants. In these three cases, the transcriptional block of IFN-induced genes is due to inhibition of ISGF-3 activation and binding. Our data suggest that the EBNA2-related IFN resistance in Burkitt's lymphoma cells acts downstream of the activation of ISGF-3.

MeSH Terms
Antigens, Viral/genetics,metabolism Blotting, Northern Burkitt Lymphoma DNA-Binding Proteins/biosynthesis,genetics,metabolism Drug Resistance/genetics Epstein-Barr Virus Nuclear Antigens Gene Expression Regulation Interferon-Stimulated Gene Factor 3 Interferon-alpha/pharmacology Transcription Factors/biosynthesis,genetics Transcription, Genetic Tumor Cells, Cultured
Chemicals
Antigens, Viral DNA-Binding Proteins Epstein-Barr Virus Nuclear Antigens Interferon-Stimulated Gene Factor 3 Interferon-alpha Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kanda K
Department of Bacteriology, Karolinska Institute, Stockholm, Sweden.
Decker T
Aman P
Wahlström M
von Gabain A
Kallin B
References (64)
64 references, click to expand
  1. 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):813-21 PMID: 6327290
  2. The Epstein-Barr virus proteins.
    Adv Cancer Res. 1988;50:95-158 PMID: 2837072
  3. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1203-7 PMID: 2919169
  4. Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction.
    J Biol Chem. 1986 Jan 5;261(1):453-9 PMID: 2934388
  5. Characterization of a second Epstein-Barr virus-determined nuclear antigen associated with the BamHI WYH region of EBV DNA.
    Int J Cancer. 1985 Mar 15;35(3):359-66 PMID: 2982749
  6. Antibodies against synthetic peptides react with the second Epstein-Barr virus-associated nuclear antigen.
    EMBO J. 1985 Jul;4(7):1813-8 PMID: 2992945
  7. An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines.
    Proc Natl Acad Sci U S A. 1986 Sep;83(17):6641-5 PMID: 3018741
  8. 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):1310-7 PMID: 3033261
  9. Cloning and chromosomal location of human genes inducible by type I interferon.
    Somat Cell Mol Genet. 1988 Sep;14(5):415-26 PMID: 3175763
  10. Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.
    Genes Dev. 1988 Apr;2(4):383-93 PMID: 3371658
  11. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
    Cell. 1988 Sep 9;54(6):903-13 PMID: 3409321
  12. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394-8 PMID: 3476954
  13. 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):829-33 PMID: 6161964
  14. Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.
    Nucleic Acids Res. 1983 Mar 11;11(5):1213-26 PMID: 6186990
  15. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis.
    Nucleic Acids Res. 1981 Dec 11;9(23):6505-25 PMID: 6275366
  16. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  17. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5 PMID: 6438633
  18. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.
    Cell. 1984 Oct;38(3):745-55 PMID: 6548414
  19. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  20. Induction and biological characterization of the Epstein-Barr virus (EBV) carried by the Jijoye lymphoma line.
    Virology. 1980 Mar;101(2):553-7 PMID: 6244705
  21. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye.
    J Virol. 1982 Dec;44(3):834-44 PMID: 6294333
  22. 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):478-84 PMID: 165958
  23. Identification of critical cis elements involved in mediating Epstein-Barr virus nuclear antigen 2-dependent activity of an enhancer located upstream of the viral BamHI C promoter.
    J Virol. 1992 May;66(5):2846-52 PMID: 1313905
  24. Inhibition of interferon-inducible gene expression by adenovirus E1A proteins: block in transcriptional complex formation.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7459-63 PMID: 1652751
  25. Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2888-92 PMID: 1707174
  26. Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.
    Mol Cell Biol. 1991 Oct;11(10):5147-53 PMID: 1833631
  27. Epstein-Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation.
    J Virol. 1991 May;65(5):2545-54 PMID: 1850028
  28. Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons.
    Mol Cell Biol. 1991 Aug;11(8):4189-95 PMID: 1906577
  29. The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization.
    J Virol. 1990 Jun;64(6):2530-6 PMID: 2159528
  30. ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555-9 PMID: 2236065
  31. Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either.
    Mol Cell Biol. 1990 Jun;10(6):2448-57 PMID: 2342456
  32. Interferons and their actions.
    Annu Rev Biochem. 1987;56:727-77 PMID: 2441659
  33. Host cell-dependent regulation of growth transformation-associated Epstein-Barr virus antigens in somatic cell hybrids.
    J Virol. 1989 Jun;63(6):2768-72 PMID: 2542588
  34. 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):1080-5 PMID: 2552313
  35. Overlapping sites for constitutive and induced DNA binding factors involved in interferon-stimulated transcription.
    EMBO J. 1989 Mar;8(3):831-9 PMID: 2721502
  36. 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):3870-8 PMID: 2824821
  37. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8693-6 PMID: 2847171
  38. Cells resistant to interferon are defective in activation of a promoter-binding factor.
    EMBO J. 1988 Dec 1;7(12):3779-83 PMID: 2974800
  39. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells.
    Nature. 1985 Feb 28-Mar 6;313(6005):812-5 PMID: 2983224
  40. Geographical prevalence of two types of Epstein-Barr virus.
    Virology. 1986 Oct 15;154(1):56-66 PMID: 3019008
  41. 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):3452-6 PMID: 3033649
  42. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  43. Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):8929-33 PMID: 3466167
  44. Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells.
    Proc Natl Acad Sci U S A. 1986 Mar;83(5):1499-503 PMID: 3485288
  45. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  46. Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon.
    J Gen Virol. 1975 Aug;28(2):207-17 PMID: 170370
  47. Epstein-Barr virus nuclear protein 2 transactivates a cis-acting CD23 DNA element.
    J Virol. 1991 Aug;65(8):4101-6 PMID: 1649318
  48. Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7913-7 PMID: 1654549
  49. Isolation of cDNA clones for the interferon-induced 67,000-dalton protein: direct induction of a family of mRNAs by human interferon-alpha and interferon-gamma.
    J Interferon Res. 1990 Jun;10(3):309-19 PMID: 1696608
  50. Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene.
    Nucleic Acids Res. 1991 Aug 25;19(16):4387-93 PMID: 1832217
  51. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene.
    J Virol. 1991 Jan;65(1):415-23 PMID: 1845900
  52. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.
    Mol Cell Biol. 1991 Jan;11(1):182-91 PMID: 1898761
  53. Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor.
    EMBO J. 1991 Apr;10(4):927-32 PMID: 1901265
  54. An Epstein-Barr virus immortalization associated gene segment interferes specifically with the IFN-induced anti-proliferative response in human B-lymphoid cell lines.
    EMBO J. 1990 Jan;9(1):147-52 PMID: 2153074
  55. Subnuclear localization and phosphorylation of Epstein-Barr virus latent infection nuclear proteins.
    Virology. 1990 Jun;176(2):563-74 PMID: 2161150
  56. Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7390-4 PMID: 2170976
  57. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator.
    Genes Dev. 1990 Oct;4(10):1753-65 PMID: 2249773
  58. Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1.
    J Virol. 1990 Jul;64(7):3407-16 PMID: 2352328
  59. Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products.
    J Virol. 1988 Jan;62(1):114-9 PMID: 2446013
  60. Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway.
    Mol Cell Biol. 1989 Nov;9(11):4605-12 PMID: 2513475
  61. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes.
    Nature. 1989 Aug 3;340(6232):393-7 PMID: 2547164
  62. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558-62 PMID: 2556717
  63. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro.
    Genes Dev. 1989 Sep;3(9):1362-71 PMID: 2606351
  64. 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):2407-18 PMID: 2821180
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.11.4930-4936.1992
Published
1992-11-00
Pages
4930-6
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360425
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/mcb.12.11.4930-4936.1992 PMC Full Text View journal details
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