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EMBO J. Sep 1987; 6(9): 2743–2751.
PMCID: PMC553698

Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells.


Recently established Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cell lines, carrying chromosomal translocations indicative of their malignant origin, have been monitored for their degree of in vitro progression towards a more 'lymphoblastoid' cell surface phenotype and growth pattern, and for their expression of three EBV latent gene products which are constitutively present in all virus-transformed normal lymphoblastoid cell lines (LCLs). BL cell lines which stably retained the original tumour biopsy phenotype on serial passage were all positive for the nuclear antigen EBNA 1 but did not express detectable amounts of two other 'transforming' proteins, EBNA 2 and the latent membrane protein (LMP). This novel pattern of EBV gene expression was also observed on direct analysis of BL biopsy tissue. All three viral proteins became detectable, however, in BL cell lines which had progressed towards a more LCL-like phenotype in vitro. This work establishes a link between B cell phenotype and the accompanying pattern of EBV latent gene expression, and identifies a novel type of EBV:cell interaction which may be unique to BL cells.

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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]
  • Aviv H, Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. [PMC free article] [PubMed]
  • Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Séguin C, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. [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]
  • Cleary ML, Epstein MA, Finerty S, Dorfman RF, Bornkamm GW, Kirkwood JK, Morgan AJ, Sklar J. Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones. Science. 1985 May 10;228(4700):722–724. [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]
  • 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]
  • Dillner J, Kallin B, Alexander H, Ernberg I, Uno M, Ono Y, Klein G, Lerner RA. 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):6641–6645. [PMC free article] [PubMed]
  • Ehlin-Henriksson B, Klein G. Distinction between Burkitt lymphoma subgroups by monoclonal antibodies: relationships between antigen expression and type of chromosomal translocation. Int J Cancer. 1984 Apr 15;33(4):459–463. [PubMed]
  • Farrell PJ, Broeze RJ, Lengyel P. Accumulation of an mRNA and protein in interferon-treated Ehrlich ascites tumour cells. Nature. 1979 Jun 7;279(5713):523–525. [PubMed]
  • Favrot MC, Philip I, Philip T, Portoukalian J, Doré JF, Lenoir GM. Distinct reactivity of Burkitt's lymphoma cell lines with eight monoclonal antibodies correlated with the ethnic origin. J Natl Cancer Inst. 1984 Oct;73(4):841–847. [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 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]
  • 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, 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]
  • Klein G. Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution. Proc Natl Acad Sci U S A. 1979 May;76(5):2442–2446. [PMC free article] [PubMed]
  • Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983 Feb;32(2):311–315. [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]
  • Mann KP, Staunton D, Thorley-Lawson DA. Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells. J Virol. 1985 Sep;55(3):710–720. [PMC free article] [PubMed]
  • McMaster GK, Carmichael GG. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. [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, Burrows SR, Castelino DJ, Kane RG, Pope JH, Rickinson AB, Alpers MP, Heywood PF. A comparison of Epstein-Barr virus-specific T-cell immunity in malaria-endemic and -nonendemic regions of Papua New Guinea. Int J Cancer. 1983 Jun 15;31(6):727–732. [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]
  • Rickinson AB, Moss DJ, Wallace LE, Rowe M, Misko IS, Epstein MA, Pope JH. Long-term T-cell-mediated immunity to Epstein-Barr virus. Cancer Res. 1981 Nov;41(11 Pt 1):4216–4221. [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, Young LS, Rowe M. 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):1310–1317. [PMC free article] [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Ritz J, Pesando JM, Notis-McConarty J, Lazarus H, Schlossman SF. A monoclonal antibody to human acute lymphoblastic leukaemia antigen. Nature. 1980 Feb 7;283(5747):583–585. [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]
  • 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]
  • 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]
  • Rowe DT, Farrell PJ, Miller G. Novel nuclear antigens recognized by human sera in lymphocytes latently infected by Epstein-Barr virus. Virology. 1987 Jan;156(1):153–162. [PubMed]
  • Rowe M, Hildreth JE, Rickinson AB, Epstein MA. 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. [PubMed]
  • Rowe M, Rooney CM, Rickinson AB, Lenoir GM, Rupani H, Moss DJ, Stein H, Epstein MA. Distinctions between endemic and sporadic forms of Epstein-Barr virus-positive Burkitt's lymphoma. Int J Cancer. 1985 Apr 15;35(4):435–441. [PubMed]
  • Rowe M, Rooney CM, Edwards CF, Lenoir GM, Rickinson AB. Epstein-Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma. Int J Cancer. 1986 Mar 15;37(3):367–373. [PubMed]
  • Rowe M, Evans HS, Young LS, Hennessy K, Kieff E, Rickinson AB. 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):1575–1586. [PubMed]
  • Rymo L. Identification of transcribed regions of Epstein-Barr virus DNA in Burkitt lymphoma-derived cells. J Virol. 1979 Oct;32(1):8–18. [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]
  • Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, Diehl V. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature. 1982 Sep 2;299(5878):65–67. [PubMed]
  • Speck SH, Pfitzner A, Strominger JL. 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):9298–9302. [PMC free article] [PubMed]
  • Stein H, Gerdes J, Schwab U, Lemke H, Diehl V, Mason DY, Bartels H, Ziegler A. Evidence for the detection of the normal counterpart of Hodgkin and Sternberg-Reed cells. Hematol Oncol. 1983 Jan-Mar;1(1):21–29. [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]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • Thorley-Lawson DA, Nadler LM, Bhan AK, Schooley RT. 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]
  • 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. [PubMed]
  • Wang F, Gregory CD, Rowe M, Rickinson AB, Wang D, Birkenbach M, Kikutani H, Kishimoto T, Kieff E. 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):3452–3456. [PMC free article] [PubMed]
  • Wiels J, Fellous M, Tursz T. Monoclonal antibody against a Burkitt lymphoma-associated antigen. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6485–6488. [PMC free article] [PubMed]
  • Yates J, Warren N, Reisman D, Sugden B. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806–3810. [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]

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