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PMID: 2154588 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Stable transfection of Epstein-Barr virus (EBV) nuclear antigen 2 in lymphoma cells containing the EBV P3HR1 genome induces expression of B-cell activation molecules CD21 and CD23.

Journal of virology ·Vol. 64 ·No. 3 ·1990-03-00 ·Pages 1002-13

Cordier M, Calender A, Billaud M, Zimber U, Rousselet G, Pavlish O, Banchereau J, Tursz T, Bornkamm G, Lenoir GM

Abstract

A set of B-cell activation molecules, including the Epstein-Barr virus (EBV) receptor CR2 (CD21) and the B-cell activation antigen CD23 (Blast2/Fc epsilon RII), is turned on by infecting EBV-negative B-lymphoma cell lines with immortalizing strains of the viruslike B95-8 (BL/B95 cells). This up regulation may represent one of the mechanisms involved in EBV-mediated B-cell immortalization. The P3HR1 nonimmortalizing strain of the virus, which is deleted for the entire Epstein-Barr nuclear antigen 2 (EBNA2) protein open reading frame, is incapable of inducing the expression of CR2 and CD23, suggesting a crucial role for EBNA2 in the activation of these molecules. In addition, lymphoma cells containing the P3HR1 genome (BL/P3HR1 cells) do not express the viral latent membrane protein (LMP), which is regularly expressed in cells infected with immortalizing viral strains. Using electroporation, we have transfected the EBNA2 gene cloned in an episomal vector into BL/P3HR1 cells and have obtained cell clones that stably express the EBNA2 protein. In these clones, EBNA2 expression was associated with an increased amount of CR2 and CD23 steady-state RNAs. Of the three species of CD23 mRNAs described, the Fc epsilon RIIa species was preferentially expressed in these EBNA2-expressing clones. An increased cell surface expression of CR2 but not of CD23 was observed, and the soluble form of CD23 molecule (SCD23) was released. We were, however, not able to detect any expression of LMP in these cell clones. These data demonstrate that EBNA2 gene is able to complement P3HR1 virus latent functions to induce the activation of CR2 and CD23 expression, and they emphasize the role of EBNA2 protein in the modulation of cellular gene implicated in B-cell proliferation and hence in EBV-mediated B-cell immortalization. Nevertheless, EBNA2 expression in BL/P3HR1 cells is not able to restore the level of CR2 and CD23 expression observed in BL/B95 cells, suggesting that other cellular or viral proteins may also have an important role in the activation of these molecules: the viral LMP seems to be a good candidate.

MeSH Terms
Antigens, CD/immunology Antigens, Differentiation, B-Lymphocyte/genetics Antigens, Viral/genetics B-Lymphocytes/immunology Cell Line Complement C3d/immunology Enzyme-Linked Immunosorbent Assay Epstein-Barr Virus Nuclear Antigens Gene Expression Genes, Viral Herpesvirus 4, Human/genetics,immunology Humans Lymphocyte Activation Lymphoma Plasmids RNA, Messenger/genetics Receptors, Complement/genetics Receptors, Complement 3d Receptors, Fc/genetics Receptors, IgE Transcription, Genetic Transfection
Chemicals
Antigens, CD Antigens, Differentiation, B-Lymphocyte Antigens, Viral Epstein-Barr Virus Nuclear Antigens RNA, Messenger Receptors, Complement Receptors, Complement 3d Receptors, Fc Receptors, IgE Complement C3d
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Cordier M
International Agency for Research on Cancer, Lyon, France.
Calender A
Billaud M
Zimber U
Rousselet G
Pavlish O
Banchereau J
Tursz T
Bornkamm G
Lenoir G M
References (53)
53 references, click to expand
  1. Simple repeat array in Epstein-Barr virus DNA encodes part of the Epstein-Barr nuclear antigen.
    Science. 1983 Jun 24;220(4604):1396-8 PMID: 6304878
  2. Epstein-Barr virus (EBV)-containing nasopharyngeal carcinoma cells express the B-cell activation antigen blast2/CD23 and low levels of the EBV receptor CR2.
    J Virol. 1989 Oct;63(10):4121-8 PMID: 2550660
  3. Immortalized B lymphocytes produce B-cell growth factor.
    Nature. 1984 Jul 12-18;310(5973):145-7 PMID: 6610833
  4. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2.
    Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510-4 PMID: 6087328
  5. 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
  6. A membrane protein encoded by Epstein-Barr virus in latent growth-transforming infection.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7207-11 PMID: 6095274
  7. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2.
    Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632-6 PMID: 6209719
  8. Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule.
    Eur J Immunol. 1985 Jan;15(1):73-6 PMID: 3155687
  9. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus.
    Mol Cell Biol. 1985 Feb;5(2):410-3 PMID: 2983194
  10. 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
  11. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor.
    Proc Natl Acad Sci U S A. 1985 Mar;82(5):1490-3 PMID: 2983347
  12. 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):3007-12 PMID: 2984280
  13. Early events in Epstein-Barr virus infection provide a model for B cell activation.
    J Exp Med. 1985 Jul 1;162(1):45-59 PMID: 2989413
  14. 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):1805-11 PMID: 2992944
  15. Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes.
    J Immunol. 1985 Nov;135(5):3068-73 PMID: 2995485
  16. Growth control of activated, synchronized murine B cells by the C3d fragment of human complement.
    Nature. 1985 Sep 19-25;317(6034):264-7 PMID: 3876511
  17. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells.
    Cell. 1985 Dec;43(3 Pt 2):831-40 PMID: 3000618
  18. Monoclonal antibody (H107) inhibiting IgE binding to Fc epsilon R(+) human lymphocytes.
    J Immunol. 1986 Aug 15;137(4):1258-63 PMID: 2942602
  19. Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5639-43 PMID: 3016712
  20. 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):5693-7 PMID: 3016714
  21. 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
  22. 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):1075-80 PMID: 2428624
  23. Molecular structure of human lymphocyte receptor for immunoglobulin E.
    Cell. 1986 Dec 5;47(5):657-65 PMID: 2877743
  24. Electric field-mediated DNA transfer: transient and stable gene expression in human and mouse lymphoid cells.
    Mol Cell Biol. 1986 Feb;6(2):703-6 PMID: 3466022
  25. Alpha-type B cell growth factor and complement component C3: their possible structural relationship.
    Curr Top Microbiol Immunol. 1986;132:98-104 PMID: 3491740
  26. An Epstein-Barr virus transcript from a latently infected, growth-transformed B-cell line encodes a highly repetitive polypeptide.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9298-302 PMID: 3025831
  27. Synergistic activation of cells by Epstein-Barr virus and B-cell growth factor.
    J Virol. 1987 Mar;61(3):774-81 PMID: 3027404
  28. A B cell-specific differentiation antigen, CD23, is a receptor for IgE (Fc epsilon R) on lymphocytes.
    J Immunol. 1987 Apr 15;138(8):2576-80 PMID: 2951441
  29. Production and characterization of a monoclonal antibody specific for the human lymphocyte low affinity receptor for IgE: CD 23 is a low affinity receptor for IgE.
    J Immunol. 1987 May 1;138(9):2970-8 PMID: 2952729
  30. 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
  31. Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells.
    J Gen Virol. 1987 Jun;68 ( Pt 6):1575-86 PMID: 2438376
  32. Generation of specific cytotoxic T cells with a fragment of the Epstein-Barr virus-encoded p63/latent membrane protein.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5384-8 PMID: 3037547
  33. The activation antigen BLAST-2, when shed, is an autocrine BCGF for normal and transformed B cells.
    EMBO J. 1987 Jun;6(6):1637-42 PMID: 3038527
  34. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells.
    EMBO J. 1987 Sep;6(9):2743-51 PMID: 2824192
  35. Selective extraction of polyoma DNA from infected mouse cell cultures.
    J Mol Biol. 1967 Jun 14;26(2):365-9 PMID: 4291934
  36. 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 PMID: 4133943
  37. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  38. 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):373-81 PMID: 6282762
  39. Stable expression in mouse cells of nuclear neoantigen after transfer of a 3.4-megadalton cloned fragment of Epstein-Barr virus DNA.
    Proc Natl Acad Sci U S A. 1982 Sep;79(18):5688-92 PMID: 6291059
  40. RNA encoded by the IR1-U2 region of Epstein-Barr virus DNA in latently infected, growth-transformed cells.
    J Virol. 1983 May;46(2):424-33 PMID: 6188862
  41. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060-4 PMID: 2825176
  42. Different patterns of Epstein-Barr virus gene expression and of cytotoxic T-cell recognition in B-cell lines infected with transforming (B95.8) or nontransforming (P3HR1) virus strains.
    J Virol. 1988 Mar;62(3):894-901 PMID: 2828684
  43. BamHI E region of the Epstein-Barr virus genome encodes three transformation-associated nuclear proteins.
    Proc Natl Acad Sci U S A. 1988 Feb;85(4):995-9 PMID: 2829223
  44. Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40).
    Eur J Immunol. 1988 Mar;18(3):349-53 PMID: 2965643
  45. A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome.
    EMBO J. 1988 Mar;7(3):769-74 PMID: 2840285
  46. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components.
    Mol Cell Biol. 1985 Aug;5(8):1822-32 PMID: 3018528
  47. Epstein-Barr virus-specific cytotoxic T-cell recognition of transfectants expressing the virus-coded latent membrane protein LMP.
    J Virol. 1988 Oct;62(10):3747-55 PMID: 2843672
  48. Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1.
    J Exp Med. 1988 Oct 1;168(4):1255-70 PMID: 2971757
  49. 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):4173-84 PMID: 2845129
  50. Characterization of a latent protein encoded by the large internal repeats and the BamHI Y fragment of the Epstein-Barr virus (EBV) genome.
    Virology. 1988 Oct;166(2):586-90 PMID: 2845663
  51. Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression.
    Cell. 1988 Nov 18;55(4):611-8 PMID: 2972386
  52. A second subunit of CD8 is expressed in human T cells.
    EMBO J. 1988 Nov;7(11):3433-9 PMID: 3145195
  53. A complete set of overlapping cosmid clones of M-ABA virus derived from nasopharyngeal carcinoma and its similarity to other Epstein-Barr virus isolates.
    Gene. 1984 Mar;27(3):279-88 PMID: 6329907
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1990-03-00
Pages
1002-13
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC249210
Subset
IM
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