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J Virol. May 1987; 61(5): 1310–1317.
PMCID: PMC254104

Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells.


Epstein-Barr virus (EBV) isolates show sequence divergence in the BamHI YH region of the genome which encodes the nuclear antigen EBNA 2, a protein thought to be involved in the initiation of virus-induced B-cell transformation; type A isolates (such as B95-8 EBV) encode a 82- to 87-kilodalton EBNA 2A protein, whereas type B isolates (such as AG876 EBV) encode an antigenically distinct 75-kilodalton EBNA 2B protein. In the present work 12 type A isolates and 8 type B isolates have been compared for their ability to transform resting human B cells in vitro into permanent lymphoblastoid cell lines. Although the kinetics of initial focus formation was not markedly dependent upon the EBNA 2 type of the transforming virus, on subsequent passage type A virus-transformed cells (type A transformants) yielded cell lines much more readily than did type B transformants. Direct comparison between the two types of transformant revealed clear differences in several aspects of growth phenotype. Compared with type A transformants, cell lines established with type B virus isolates consistently displayed an unusual growth pattern with poor survival of individual cells shed from lymphoblastoid clumps, a lower growth rate and a greater sensitivity to seeding at limiting dilutions, and a significantly lower saturation density that could not be corrected by supplementation of the medium with culture supernatant containing B-cell growth factors. This is the first direct evidence that, in EBV-transformed B-cell lines, the EBNA 2 protein plays a continuing role in determining the cellular growth phenotype.

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  • Adldinger HK, Delius H, Freese UK, Clarke J, Bornkamm GW. A putative transforming gene of Jijoye virus differs from that of Epstein-Barr virus prototypes. Virology. 1985 Mar;141(2):221–234. [PubMed]
  • Bornkamm GW, Hudewentz J, Freese UK, Zimber U. Deletion of the nontransforming Epstein-Barr virus strain P3HR-1 causes fusion of the large internal repeat to the DSL region. J Virol. 1982 Sep;43(3):952–968. [PMC free article] [PubMed]
  • Burnette WN. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. [PubMed]
  • Dambaugh T, Hennessy K, Chamnankit L, Kieff E. 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):7632–7636. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Dillner J, Kallin B, Ehlin-Henriksson B, Timar L, Klein G. 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):359–366. [PubMed]
  • Gordon J, Ley SC, Melamed MD, Aman P, Hughes-Jones NC. Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus. J Exp Med. 1984 May 1;159(5):1554–1559. [PMC free article] [PubMed]
  • Gordon J, Ley SC, Melamed MD, English LS, Hughes-Jones NC. Immortalized B lymphocytes produce B-cell growth factor. Nature. 1984 Jul 12;310(5973):145–147. [PubMed]
  • Gordon J, Walker L, Guy G, Brown G, Rowe M, Rickinson A. Control of human B-lymphocyte replication. II. Transforming Epstein-Barr virus exploits three distinct viral signals to undermine three separate control points in B-cell growth. Immunology. 1986 Aug;58(4):591–595. [PMC free article] [PubMed]
  • Griffith IP. Immediate visualization of proteins in dodecyl sulfate-polyacrylamide gels by prestaining with Remazol dyes. Anal Biochem. 1972 Apr;46(2):402–412. [PubMed]
  • Henle G, Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Henle W, Henle G, Zajac BA, Pearson G, Waubke R, Scriba M. Differential reactivity of human serums with early antigens induced by Epstein-Barr virus. Science. 1970 Jul 10;169(3941):188–190. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Hennessy K, Wang F, Bushman EW, 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. [PMC free article] [PubMed]
  • Kallin B, Dillner J, Ernberg I, Ehlin-Henriksson B, Rosén A, Henle W, Henle G, Klein G. Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1499–1503. [PMC free article] [PubMed]
  • King W, Dambaugh T, Heller M, Dowling J, Kieff E. Epstein-Barr virus DNA XII. A variable region of the Epstein-Barr virus genome is included in the P3HR-1 deletion. J Virol. 1982 Sep;43(3):979–986. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Lenoir GM, Vuillaume M, Bonnardel C. The use of lymphomatous and lymphoblastoid cell lines in the study of Burkitt's lymphoma. IARC Sci Publ. 1985;(60):309–318. [PubMed]
  • Miller G, Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Moss DJ, Rickinson AB, Pope JH. Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes. Int J Cancer. 1978 Dec;22(6):662–668. [PubMed]
  • Moss DJ, Sculley TB, Pope JH. Induction of Epstein-Barr virus nuclear antigens. J Virol. 1986 Jun;58(3):988–990. [PMC free article] [PubMed]
  • Mueller-Lantzsch N, Lenoir GM, Sauter M, Takaki K, Béchet JM, Kuklik-Roos C, Wunderlich D, Bornkamm GW. 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. [PMC free article] [PubMed]
  • Pizzo PA, Magrath IT, Chattopadhyay SK, Biggar RJ, Gerber P. A new tumour-derived transforming strain of Epstein-Barr virus. Nature. 1978 Apr 13;272(5654):629–631. [PubMed]
  • Pope JH, Horne MK, 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. [PubMed]
  • Rabson M, Gradoville L, Heston L, Miller G. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye. J Virol. 1982 Dec;44(3):834–844. [PMC free article] [PubMed]
  • Rawlins DR, Milman G, Hayward SD, Hayward GS. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985 Oct;42(3):859–868. [PubMed]
  • Reisman D, Yates J, Sugden B. 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):1822–1832. [PMC free article] [PubMed]
  • Rickinson AB, Rowe M, Hart IJ, Yao QY, Henderson LE, Rabin H, Epstein MA. T-cell-mediated regression of "spontaneous" and of Epstein-Barr virus-induced B-cell transformation in vitro: studies with cyclosporin A. Cell Immunol. 1984 Sep;87(2):646–658. [PubMed]
  • Rickinson AB, Yao QY, Wallace LE. The Epstein-Barr virus as a model of virus-host interactions. Br Med Bull. 1985 Jan;41(1):75–79. [PubMed]
  • Rooney CM, Gregory CD, Rowe M, Finerty S, Edwards C, Rupani H, Rickinson AB. Endemic Burkitt's lymphoma: phenotypic analysis of tumor biopsy cells and of derived tumor cell lines. J Natl Cancer Inst. 1986 Sep;77(3):681–687. [PubMed]
  • Rooney CM, Rickinson AB, Moss DJ, Lenoir GM, Epstein MA. Paired Epstein-Barr virus-carrying lymphoma and lymphoblastoid cell lines from Burkitt's lymphoma patients: comparative sensitivity to non-specific and to allo-specific cytotoxic responses in vitro. Int J Cancer. 1984 Sep 15;34(3):339–348. [PubMed]
  • Rowe D, Heston L, Metlay J, Miller G. Identification and expression of a nuclear antigen from the genomic region of the Jijoye strain of Epstein-Barr virus that is missing in its nonimmortalizing deletion mutant, P3HR-1. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7429–7433. [PMC free article] [PubMed]
  • Rowe DT, Rowe M, Evan GI, Wallace LE, Farrell PJ, Rickinson AB. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells. EMBO J. 1986 Oct;5(10):2599–2607. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Skare J, Farley J, Strominger JL, Fresen KO, Cho MS, 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. [PMC free article] [PubMed]
  • Strnad BC, Schuster TC, Hopkins RF, 3rd, Neubauer RH, Rabin H. Identification of an Epstein-Barr virus nuclear antigen by fluoroimmunoelectrophoresis and radioimmunoelectrophoresis. J Virol. 1981 Jun;38(3):996–1004. [PMC free article] [PubMed]
  • Summers WP, Grogan EA, Shedd D, Robert M, Liu CR, Miller G. 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):5688–5692. [PMC free article] [PubMed]
  • Yates JL, Warren N, Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature. 313(6005):812–815. [PubMed]
  • Zimber U, Adldinger HK, Lenoir GM, Vuillaume M, Knebel-Doeberitz MV, Laux G, Desgranges C, Wittmann P, Freese UK, Schneider U, et al. Geographical prevalence of two types of Epstein-Barr virus. Virology. 1986 Oct 15;154(1):56–66. [PubMed]

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