Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Jan;17(1):364–377. doi: 10.1128/mcb.17.1.364

Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs.

B C Schaefer 1, J L Strominger 1, S H Speck 1
PMCID: PMC231761  PMID: 8972217

Abstract

Epstein-Barr virus (EBV) is capable of adopting three distinct forms of latency: the type III latency program, in which six EBV-encoded nuclear antigens (EBNAs) are expressed, and the type I and type II latency programs, in which only a single viral nuclear protein, EBNA1, is produced. Several groups have reported heavy CpG methylation of the EBV genome in Burkitt's lymphoma cell lines which maintain type I latency, and loss of viral genome methylation in tumor cell lines has been correlated with a switch to type III latency. Here, evidence that the type III latency program must be inactivated by methylation to allow EBV to enter the type I or type II restricted latency program is provided. The data demonstrates that the EBNA1 gene promoter, Qp, active in types I and II latency, is encompassed by a CpG island which is protected from methylation. CpG methylation inactivates the type III latency program and consequently allows the type I or II latency program to operate by alleviating EBNA1-mediated repression of Qp. Methylation of the type III latency EBNA gene promoter, Cp, appears to be essential to prevent type III latency, since EBNA1 is expressed in all latently infected cells and, as shown here, is the only viral antigen required for activation of Cp. EBV is thus a pathogen which subverts host-cell-determined methylation to regulate distinct genetic programs.

Full Text

The Full Text of this article is available as a PDF (464.7 KB).

Selected References

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

  1. Altiok E., Minarovits J., Hu L. F., Contreras-Brodin B., Klein G., Ernberg I. Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):905–909. doi: 10.1073/pnas.89.3.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barlow D. P. Methylation and imprinting: from host defense to gene regulation? Science. 1993 Apr 16;260(5106):309–310. doi: 10.1126/science.8469984. [DOI] [PubMed] [Google Scholar]
  3. Bird A. P. Functions for DNA methylation in vertebrates. Cold Spring Harb Symp Quant Biol. 1993;58:281–285. doi: 10.1101/sqb.1993.058.01.033. [DOI] [PubMed] [Google Scholar]
  4. Brandeis M., Frank D., Keshet I., Siegfried Z., Mendelsohn M., Nemes A., Temper V., Razin A., Cedar H. Sp1 elements protect a CpG island from de novo methylation. Nature. 1994 Sep 29;371(6496):435–438. doi: 10.1038/371435a0. [DOI] [PubMed] [Google Scholar]
  5. Brooks L., Yao Q. Y., Rickinson A. B., Young L. S. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol. 1992 May;66(5):2689–2697. doi: 10.1128/jvi.66.5.2689-2697.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Clark S. J., Harrison J., Paul C. L., Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 1994 Aug 11;22(15):2990–2997. doi: 10.1093/nar/22.15.2990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deacon E. M., Pallesen G., Niedobitek G., Crocker J., Brooks L., Rickinson A. B., Young L. S. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med. 1993 Feb 1;177(2):339–349. doi: 10.1084/jem.177.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deng W. P., Nickoloff J. A. Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. Anal Biochem. 1992 Jan;200(1):81–88. doi: 10.1016/0003-2697(92)90280-k. [DOI] [PubMed] [Google Scholar]
  10. Ernberg I., Falk K., Minarovits J., Busson P., Tursz T., Masucci M. G., Klein G. The role of methylation in the phenotype-dependent modulation of Epstein-Barr nuclear antigen 2 and latent membrane protein genes in cells latently infected with Epstein-Barr virus. J Gen Virol. 1989 Nov;70(Pt 11):2989–3002. doi: 10.1099/0022-1317-70-11-2989. [DOI] [PubMed] [Google Scholar]
  11. Evans T. J., Jacquemin M. G., Farrell P. J. Efficient EBV superinfection of group I Burkitt's lymphoma cells distinguishes requirements for expression of the Cp viral promoter and can activate the EBV productive cycle. Virology. 1995 Feb 1;206(2):866–877. doi: 10.1006/viro.1995.1009. [DOI] [PubMed] [Google Scholar]
  12. Flemington E. K., Lytle J. P., Cayrol C., Borras A. M., Speck S. H. DNA-binding-defective mutants of the Epstein-Barr virus lytic switch activator Zta transactivate with altered specificities. Mol Cell Biol. 1994 May;14(5):3041–3052. doi: 10.1128/mcb.14.5.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fåhraeus R., Fu H. L., Ernberg I., Finke J., Rowe M., Klein G., Falk K., Nilsson E., Yadav M., Busson P. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 1988 Sep 15;42(3):329–338. doi: 10.1002/ijc.2910420305. [DOI] [PubMed] [Google Scholar]
  14. Gilligan K., Sato H., Rajadurai P., Busson P., Young L., Rickinson A., Tursz T., Raab-Traub N. Novel transcription from the Epstein-Barr virus terminal EcoRI fragment, DIJhet, in a nasopharyngeal carcinoma. J Virol. 1990 Oct;64(10):4948–4956. doi: 10.1128/jvi.64.10.4948-4956.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gregory C. D., Rowe M., Rickinson A. B. Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt's lymphoma cell line. J Gen Virol. 1990 Jul;71(Pt 7):1481–1495. doi: 10.1099/0022-1317-71-7-1481. [DOI] [PubMed] [Google Scholar]
  17. Groudine M., Eisenman R., Weintraub H. Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature. 1981 Jul 23;292(5821):311–317. doi: 10.1038/292311a0. [DOI] [PubMed] [Google Scholar]
  18. Hayashi M., Furuichi T., Ren S., Isogai E., Nonoyama M., Namioka S. Enhancement of mRNA synthesis from Marek's disease virus genome in the lymphoblastoid cell line, MDCC-MSB1, by 5-azacytidine. J Vet Med Sci. 1994 Apr;56(2):287–291. doi: 10.1292/jvms.56.287. [DOI] [PubMed] [Google Scholar]
  19. Herbst H., Dallenbach F., Hummel M., Niedobitek G., Pileri S., Müller-Lantzsch N., Stein H. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4766–4770. doi: 10.1073/pnas.88.11.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hinuma Y., Konn M., Yamaguchi J., Wudarski D. J., Blakeslee J. R., Jr, Grace J. T., Jr Immunofluorescence and herpes-type virus particles in the P3HR-1 Burkitt lymphoma cell line. J Virol. 1967 Oct;1(5):1045–1051. doi: 10.1128/jvi.1.5.1045-1051.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hitt M. M., Allday M. J., Hara T., Karran L., Jones M. D., Busson P., Tursz T., Ernberg I., Griffin B. E. EBV gene expression in an NPC-related tumour. EMBO J. 1989 Sep;8(9):2639–2651. doi: 10.1002/j.1460-2075.1989.tb08404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Honess R. W., Gompels U. A., Barrell B. G., Craxton M., Cameron K. R., Staden R., Chang Y. N., Hayward G. S. Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes. J Gen Virol. 1989 Apr;70(Pt 4):837–855. doi: 10.1099/0022-1317-70-4-837. [DOI] [PubMed] [Google Scholar]
  23. Jansson A., Masucci M., Rymo L. Methylation of discrete sites within the enhancer region regulates the activity of the Epstein-Barr virus BamHI W promoter in Burkitt lymphoma lines. J Virol. 1992 Jan;66(1):62–69. doi: 10.1128/jvi.66.1.62-69.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jin X. W., Speck S. H. 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):2846–2852. doi: 10.1128/jvi.66.5.2846-2852.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones C. H., Hayward S. D., Rawlins D. R. Interaction of the lymphocyte-derived Epstein-Barr virus nuclear antigen EBNA-1 with its DNA-binding sites. J Virol. 1989 Jan;63(1):101–110. doi: 10.1128/jvi.63.1.101-110.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jones K., Rivera C., Sgadari C., Franklin J., Max E. E., Bhatia K., Tosato G. Infection of human endothelial cells with Epstein-Barr virus. J Exp Med. 1995 Nov 1;182(5):1213–1221. doi: 10.1084/jem.182.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jähner D., Jaenisch R. Chromosomal position and specific demethylation in enhancer sequences of germ line-transmitted retroviral genomes during mouse development. Mol Cell Biol. 1985 Sep;5(9):2212–2220. doi: 10.1128/mcb.5.9.2212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jähner D., Stuhlmann H., Stewart C. L., Harbers K., Löhler J., Simon I., Jaenisch R. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982 Aug 12;298(5875):623–628. doi: 10.1038/298623a0. [DOI] [PubMed] [Google Scholar]
  29. Kanamori A., Ikuta K., Ueda S., Kato S., Hirai K. Methylation of Marek's disease virus DNA in chicken T-lymphoblastoid cell lines. J Gen Virol. 1987 May;68(Pt 5):1485–1490. doi: 10.1099/0022-1317-68-5-1485. [DOI] [PubMed] [Google Scholar]
  30. Karlin S., Doerfler W., Cardon L. R. Why is CpG suppressed in the genomes of virtually all small eukaryotic viruses but not in those of large eukaryotic viruses? J Virol. 1994 May;68(5):2889–2897. doi: 10.1128/jvi.68.5.2889-2897.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Karlin S., Mocarski E. S., Schachtel G. A. Molecular evolution of herpesviruses: genomic and protein sequence comparisons. J Virol. 1994 Mar;68(3):1886–1902. doi: 10.1128/jvi.68.3.1886-1902.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Klein G., Dombos L., Gothoskar B. Sensitivity of Epstein-Barr virus (EBV) producer and non-producer human lymphoblastoid cell lines to superinfection with EB-virus. Int J Cancer. 1972 Jul 15;10(1):44–57. doi: 10.1002/ijc.2910100108. [DOI] [PubMed] [Google Scholar]
  33. Klein G. Epstein-Barr virus strategy in normal and neoplastic B cells. Cell. 1994 Jun 17;77(6):791–793. doi: 10.1016/0092-8674(94)90125-2. [DOI] [PubMed] [Google Scholar]
  34. Kruczek I., Doerfler W. The unmethylated state of the promoter/leader and 5'-regions of integrated adenovirus genes correlates with gene expression. EMBO J. 1982;1(4):409–414. doi: 10.1002/j.1460-2075.1982.tb01183.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Laird P. W., Jaenisch R. DNA methylation and cancer. Hum Mol Genet. 1994;3(Spec No):1487–1495. doi: 10.1093/hmg/3.suppl_1.1487. [DOI] [PubMed] [Google Scholar]
  36. Langner K. D., Vardimon L., Renz D., Doerfler W. DNA methylation of three 5' C-C-G-G 3' sites in the promoter and 5' region inactivate the E2a gene of adenovirus type 2. Proc Natl Acad Sci U S A. 1984 May;81(10):2950–2954. doi: 10.1073/pnas.81.10.2950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lear A. L., Rowe M., Kurilla M. G., Lee S., Henderson S., Kieff E., Rickinson A. B. The Epstein-Barr virus (EBV) nuclear antigen 1 BamHI F promoter is activated on entry of EBV-transformed B cells into the lytic cycle. J Virol. 1992 Dec;66(12):7461–7468. doi: 10.1128/jvi.66.12.7461-7468.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lerman M. I., Sakai A., Yao K. T., Colburn N. H. DNA sequences in human nasopharyngeal carcinoma cells that specify susceptibility to tumor promoter-induced neoplastic transformation. Carcinogenesis. 1987 Jan;8(1):121–127. doi: 10.1093/carcin/8.1.121. [DOI] [PubMed] [Google Scholar]
  39. Li E., Beard C., Jaenisch R. Role for DNA methylation in genomic imprinting. Nature. 1993 Nov 25;366(6453):362–365. doi: 10.1038/366362a0. [DOI] [PubMed] [Google Scholar]
  40. Li Q. X., Young L. S., Niedobitek G., Dawson C. W., Birkenbach M., Wang F., Rickinson A. B. Epstein-Barr virus infection and replication in a human epithelial cell system. Nature. 1992 Mar 26;356(6367):347–350. doi: 10.1038/356347a0. [DOI] [PubMed] [Google Scholar]
  41. Macleod D., Charlton J., Mullins J., Bird A. P. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 1994 Oct 1;8(19):2282–2292. doi: 10.1101/gad.8.19.2282. [DOI] [PubMed] [Google Scholar]
  42. Masucci M. G., Contreras-Salazar B., Ragnar E., Falk K., Minarovits J., Ernberg I., Klein G. 5-Azacytidine up regulates the expression of Epstein-Barr virus nuclear antigen 2 (EBNA-2) through EBNA-6 and latent membrane protein in the Burkitt's lymphoma line rael. J Virol. 1989 Jul;63(7):3135–3141. doi: 10.1128/jvi.63.7.3135-3141.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Merlo A., Herman J. G., Mao L., Lee D. J., Gabrielson E., Burger P. C., Baylin S. B., Sidransky D. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995 Jul;1(7):686–692. doi: 10.1038/nm0795-686. [DOI] [PubMed] [Google Scholar]
  44. Milman G., Hwang E. S. Epstein-Barr virus nuclear antigen forms a complex that binds with high concentration dependence to a single DNA-binding site. J Virol. 1987 Feb;61(2):465–471. doi: 10.1128/jvi.61.2.465-471.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Minarovits J., Hu L. F., Marcsek Z., Minarovits-Kormuta S., Klein G., Ernberg I. RNA polymerase III-transcribed EBER 1 and 2 transcription units are expressed and hypomethylated in the major Epstein-Barr virus-carrying cell types. J Gen Virol. 1992 Jul;73(Pt 7):1687–1692. doi: 10.1099/0022-1317-73-7-1687. [DOI] [PubMed] [Google Scholar]
  46. Minarovits J., Hu L. F., Minarovits-Kormuta S., Klein G., Ernberg I. Sequence-specific methylation inhibits the activity of the Epstein-Barr virus LMP 1 and BCR2 enhancer-promoter regions. Virology. 1994 May 1;200(2):661–667. doi: 10.1006/viro.1994.1229. [DOI] [PubMed] [Google Scholar]
  47. Miyashita E. M., Yang B., Lam K. M., Crawford D. H., Thorley-Lawson D. A. A novel form of Epstein-Barr virus latency in normal B cells in vivo. Cell. 1995 Feb 24;80(4):593–601. doi: 10.1016/0092-8674(95)90513-8. [DOI] [PubMed] [Google Scholar]
  48. Murray R. J., Kurilla M. G., Brooks J. M., Thomas W. A., Rowe M., Kieff E., Rickinson A. B. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med. 1992 Jul 1;176(1):157–168. doi: 10.1084/jem.176.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Nonkwelo C., Skinner J., Bell A., Rickinson A., Sample J. Transcription start sites downstream of the Epstein-Barr virus (EBV) Fp promoter in early-passage Burkitt lymphoma cells define a fourth promoter for expression of the EBV EBNA-1 protein. J Virol. 1996 Jan;70(1):623–627. doi: 10.1128/jvi.70.1.623-627.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Nonoyama M., Tanaka A., Silver S., Glaser R. Transcription of Epstein-Barr virus genomes in human lymphoblastoid cells and in somatic-cell hybrids of Burkitt's lymphoma. IARC Sci Publ. 1978;(24 Pt 1):559–563. [PubMed] [Google Scholar]
  51. Pallesen G., Hamilton-Dutoit S. J., Rowe M., Young L. S. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9;337(8737):320–322. doi: 10.1016/0140-6736(91)90943-j. [DOI] [PubMed] [Google Scholar]
  52. Paterson R. L., Kelleher C. A., Streib J. E., Amankonah T. D., Xu J. W., Jones J. F., Gelfand E. W. Activation of human thymocytes after infection by EBV. J Immunol. 1995 Feb 1;154(3):1440–1449. [PubMed] [Google Scholar]
  53. Puglielli M. T., Woisetschlaeger M., Speck S. H. oriP is essential for EBNA gene promoter activity in Epstein-Barr virus-immortalized lymphoblastoid cell lines. J Virol. 1996 Sep;70(9):5758–5768. doi: 10.1128/jvi.70.9.5758-5768.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Raizis A. M., Schmitt F., Jost J. P. A bisulfite method of 5-methylcytosine mapping that minimizes template degradation. Anal Biochem. 1995 Mar 20;226(1):161–166. doi: 10.1006/abio.1995.1204. [DOI] [PubMed] [Google Scholar]
  55. Razin A., Cedar H. DNA methylation and gene expression. Microbiol Rev. 1991 Sep;55(3):451–458. doi: 10.1128/mr.55.3.451-458.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Robertson K. D., Hayward S. D., Ling P. D., Samid D., Ambinder R. F. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial. Mol Cell Biol. 1995 Nov;15(11):6150–6159. doi: 10.1128/mcb.15.11.6150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Rooney C. M., Rowe M., Wallace L. E., Rickinson A. B. Epstein-Barr virus-positive Burkitt's lymphoma cells not recognized by virus-specific T-cell surveillance. Nature. 1985 Oct 17;317(6038):629–631. doi: 10.1038/317629a0. [DOI] [PubMed] [Google Scholar]
  58. Rowe M., Lear A. L., Croom-Carter D., Davies A. H., Rickinson A. B. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992 Jan;66(1):122–131. doi: 10.1128/jvi.66.1.122-131.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rowe M., Rowe D. T., Gregory C. D., Young L. S., Farrell P. J., Rupani H., Rickinson A. B. 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):2743–2751. doi: 10.1002/j.1460-2075.1987.tb02568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sample J., Brooks L., Sample C., Young L., Rowe M., Gregory C., Rickinson A., Kieff E. Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6343–6347. doi: 10.1073/pnas.88.14.6343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sample J., Henson E. B., Sample C. The Epstein-Barr virus nuclear protein 1 promoter active in type I latency is autoregulated. J Virol. 1992 Aug;66(8):4654–4661. doi: 10.1128/jvi.66.8.4654-4661.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sato H., Takimoto T., Tanaka S., Ogura H., Shiraishi K., Tanaka J. Cytopathic effects induced by Epstein-Barr virus replication in epithelial nasopharyngeal carcinoma hybrid cells. J Virol. 1989 Aug;63(8):3555–3559. doi: 10.1128/jvi.63.8.3555-3559.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schaefer B. C., Strominger J. L., Speck S. H. A simple reverse transcriptase PCR assay to distinguish EBNA1 gene transcripts associated with type I and II latency from those arising during induction of the viral lytic cycle. J Virol. 1996 Nov;70(11):8204–8208. doi: 10.1128/jvi.70.11.8204-8208.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Schaefer B. C., Strominger J. L., Speck S. H. Redefining the Epstein-Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10565–10569. doi: 10.1073/pnas.92.23.10565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Schaefer B. C., Strominger J. L., Speck S. H. The Epstein-Barr virus BamHI F promoter is an early lytic promoter: lack of correlation with EBNA 1 gene transcription in group 1 Burkitt's lymphoma cell lines. J Virol. 1995 Aug;69(8):5039–5047. doi: 10.1128/jvi.69.8.5039-5047.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Schaefer B. C., Woisetschlaeger M., Strominger J. L., Speck S. H. Exclusive expression of Epstein-Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6550–6554. doi: 10.1073/pnas.88.15.6550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Schlager S., Speck S. H., Woisetschläger M. Transcription of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene occurs before induction of the BCR2 (Cp) EBNA gene promoter during the initial stages of infection in B cells. J Virol. 1996 Jun;70(6):3561–3570. doi: 10.1128/jvi.70.6.3561-3570.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Schweizer M., Fleps U., Jäckle A., Renne R., Turek R., Neumann-Haefelin D. Simian foamy virus type 3 (SFV-3) in latently infected Vero cells: reactivation by demethylation of proviral DNA. Virology. 1993 Feb;192(2):663–666. doi: 10.1006/viro.1993.1084. [DOI] [PubMed] [Google Scholar]
  69. Shibata D., Weiss L. M. Epstein-Barr virus-associated gastric adenocarcinoma. Am J Pathol. 1992 Apr;140(4):769–774. [PMC free article] [PubMed] [Google Scholar]
  70. Shimizu N., Tanabe-Tochikura A., Kuroiwa Y., Takada K. Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt's lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV. J Virol. 1994 Sep;68(9):6069–6073. doi: 10.1128/jvi.68.9.6069-6073.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Speck S. H., Pfitzner A., Strominger J. L. 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. doi: 10.1073/pnas.83.24.9298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  73. Takada K., Horinouchi K., Ono Y., Aya T., Osato T., Takahashi M., Hayasaka S. An Epstein-Barr virus-producer line Akata: establishment of the cell line and analysis of viral DNA. Virus Genes. 1991 Apr;5(2):147–156. doi: 10.1007/BF00571929. [DOI] [PubMed] [Google Scholar]
  74. Takimoto T., Kamide M., Umeda R. Establishment of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA)-positive nasopharyngeal carcinoma hybrid cell line (NPC-KT). Arch Otorhinolaryngol. 1984;239(1):87–92. doi: 10.1007/BF00454266. [DOI] [PubMed] [Google Scholar]
  75. Takimoto T. [Experimental studies on viral etiology of Epstein-Barr (EBV) in nasopharyngeal carcinoma (NPC):establishment of EBV infection on human epithelial derived from nasopharyngeal tissue (author's transl)]. Nihon Jibiinkoka Gakkai Kaiho. 1979 Feb 20;82(2):119–135. doi: 10.3950/jibiinkoka.82.119. [DOI] [PubMed] [Google Scholar]
  76. Wang F., Marchini A., Kieff E. Epstein-Barr virus (EBV) recombinants: use of positive selection markers to rescue mutants in EBV-negative B-lymphoma cells. J Virol. 1991 Apr;65(4):1701–1709. doi: 10.1128/jvi.65.4.1701-1709.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Woisetschlaeger M., Strominger J. L., Speck S. H. Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6498–6502. doi: 10.1073/pnas.86.17.6498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Woisetschlaeger M., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. H. Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1725–1729. doi: 10.1073/pnas.87.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES