1887

Abstract

The switch from latency to a productive cycle in Epstein–Barr virus (EBV)-infected B cells proliferating is thought to be due to the transcriptional activation of two viral genes, BZLF1 and BRLF1, encoding two transcription factors called EB1 and R respectively. However, a third gene, BRRF1 is contained in the BZLF1/BRLF1 locus, overlapping with BRLF1 but in inverse orientation. We have characterized the 5′ end of the BRRF1 mRNA and the promoter, PNa, at which BRRF1 pre-mRNA is initiated. We show that although a single BRRF1 mRNA species is induced by 12--tetradecanoylphorbol 13-acetate/sodium butyrate in several EBV-infected B cell lines, in Akata cells treated with anti-IgG two BRRF1 mRNAs can be detected. Transcription initiated at the BRRF1 promoter was activated by EB1 but not by R, and EB1-binding sites which contribute to the EB1-activated transcription have been mapped to between positions −469 and +1. A 34 kDa protein could be translated from the BRRF1 mRNA both and , and was found predominantly in the nucleus of HeLa cells transfected with a BRRF1 expression vector. Thus there are three promoters in the region of the EBV chromatin containing the BZLF1/BRLF1 genes, two of which, PZ and PNa, potentially share regulatory elements.

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2000-07-01
2021-07-28
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References

  1. Baer, R., Bankier, A., Biggin, M., Deininger, P., Farrell, P., Gibson, T., Hatfull, G., Hudson, G., Satchwell, S., Deguin, C., Tuffnell, P. & Barrell, B. (1984). DNA sequence and expression of the B95-8 Epstein–Barr virus genome. Nature 310, 207-211.[CrossRef] [Google Scholar]
  2. Chang, Y.-N., Dong, D. L.-Y., Hayward, G. S. & Hayward, D. (1990). The Epstein–Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. Journal of Virology 64, 3358-3369. [Google Scholar]
  3. Chang, P. J., Chang, Y. S. & Liu, S. T. (1998). Role of Rta in the translation of bicistronic BZLF1 of Epstein–Barr virus. Journal of Virology 72, 5128-5136. [Google Scholar]
  4. Chevallier-Greco, A., Manet, E., Chavrier, P., Mosnier, C., Daillie, J. & Sergeant, A. (1986). Both Epstein–Barr virus (EBV) encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO Journal 5, 3243-3249. [Google Scholar]
  5. Chevallier-Greco, A., Gruffat, H., Manet, E., Calender, A. & Sergeant, A. (1989). The EBV DR enhancer contains two functionally different domains: domain A is constitutive and cell specific, domain B is transactivated by the EBV early protein R. Journal of Virology 63, 615-623. [Google Scholar]
  6. Cho, M. & Tran, V. (1993). A concatenated form of Epstein–Barr viral DNA in lymphoblastoid cell lines induced by transfection with BZLF1. Virology 194, 838-842.[CrossRef] [Google Scholar]
  7. Countryman, J. & Miller, G. (1985). Activation of expression of latent Epstein–Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA. Proceedings of the National Academy of Sciences, USA 82, 4085-4089.[CrossRef] [Google Scholar]
  8. Countryman, J. K., Jenson, H., Grogan, E. & Miller, G. (1986). A 2·7-kb rearranged DNA fragment from Epstein–Barr virus capable of disruption of latency. Cancer Cells 4, 517-523. [Google Scholar]
  9. Farrell, P. J., Rowe, D. T., Rooney, C. M. & Kouzarides, T. (1989). Epstein–Barr virus BZLF1 transactivator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO Journal 8, 127-132. [Google Scholar]
  10. Flemington, E. & Speck, S. H. (1990). Autoregulation of Epstein–Barr virus putative switch gene BZLF1. Journal of Virology 64, 1227-1232. [Google Scholar]
  11. Francis, A., Ragoczy, T., Gradoville, L., Heston, L., El-Guindy, A., Endo, Y. & Miller, G. (1999). Amino acid substitutions reveal distinct functions of serine 186 of the ZEBRA protein in activation of early lytic cycle genes and synergy with the Epstein–Barr virus R transactivator. Journal of Virology 73, 4543-4551. [Google Scholar]
  12. Furnari, F. B., Zacny, V., Quinlivan, E. B., Kenney, S. & Pagano, J. S. (1994). RAZ, an Epstein–Barr virus transdominant repressor that modulates the viral reactivation mechanism. Journal of Virology 68, 1827-1836. [Google Scholar]
  13. Gruffat, H., Manet, E., Rigolet, A. & Sergeant, A. (1990). The enhancer factor R of Epstein–Barr virus (EBV) is a sequence-specific DNA binding protein. Nucleic Acids Research 18, 6835-6843.[CrossRef] [Google Scholar]
  14. Hammerschmidt, W. & Sugden, B. (1988). Identification and characterization of ORIlyt, a lytic origin of replication of the Epstein–Barr virus. Cell 55, 427-433.[CrossRef] [Google Scholar]
  15. Hardwick, J. M., Lieberman, P. M. & Hayward, D. (1988). A new Epstein–Barr virus transactivator, R, induces expression of a cytoplasmic early antigen. Journal of Virology 62, 2274-2284. [Google Scholar]
  16. Kieff, E. (1996). Epstein–Barr virus and its replication. In Fields Virology, pp. 2343-2395. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. Philadelphia: Lippincott–Raven.
  17. Le Roux, F., Sergeant, A. & Corbo, L. (1996). Epstein–Barr virus (EBV) EB1/Zta protein provided in trans and competent for the activation of productive cycle genes does not activate the BZLF1 gene in the EBV genome. Journal of General Virology 77, 501-509.[CrossRef] [Google Scholar]
  18. Lieberman, P. M. & Berk, A. J. (1990). In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein–Barr virus Zta protein. Journal of Virology 64, 2560-2568. [Google Scholar]
  19. Luka, J., Kallin, B. & Klein, G. (1979). Induction of the Epstein–Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology 94, 228-231.[CrossRef] [Google Scholar]
  20. Manet, E., Gruffat, H., Trescol-Biemont, M.-C., Moreno, N., Chambard, P., Giot, J.-F. & Sergeant, A. (1989). Epstein–Barr virus bicistronic mRNA generated by facultative splicing code for two transcriptional transactivators. EMBO Journal 8, 1819-1826. [Google Scholar]
  21. Manet, E., Allera, C., Gruffat, H., Mikaelian, I., Rigolet, A. & Sergeant, A. (1993). The acidic activation domain of the Epstein–Barr virus transcription factor R interacts in vitro with both TBP and TFIIB and is cell-specifically potentiated by a proline-rich region. Gene Expression 3, 48-58. [Google Scholar]
  22. Rooney, C. M., Rowe, D. T., Ragot, T. & Farrell, P. J. (1989). The spliced BZLF1 gene of Epstein–Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. Journal of Virology 63, 3109-3116. [Google Scholar]
  23. Schepers, A. P. D. & Hammerschmidt, W. (1993). Transcription factor with homology to the AP1 family links RNA transcription and DNA replication in the lytic cycle of Epstein–Barr virus. EMBO Journal 12, 3921-3929. [Google Scholar]
  24. Schwarzmann, F., Jager, M., Prang, N. & Wolf, H. (1998). The control of lytic replication of Epstein–Barr virus in B lymphocytes (Review). International Journal of Molecular Medicine 1, 137-142. [Google Scholar]
  25. Segouffin, C., Gruffat, H. & Sergeant, A. (1996). Repression by RAZ of Epstein–Barr virus bZIP transcription factor EB1 is dimerization independent. Journal of General Virology 77, 1529-1536.[CrossRef] [Google Scholar]
  26. Takada, K. & Ono, Y. (1989). Synchronous and sequential activation of latently infected Epstein–Barr virus genomes. Journal of Virology 63, 445-449. [Google Scholar]
  27. Urier, G., Buisson, M., Chambard, P. & Sergeant, A. (1989). The Epstein–Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites. EMBO Journal 8, 1447-1453. [Google Scholar]
  28. zur Hausen, H., O’Neil, F. J., Freese, U. K. & Hecker, E. (1978). Persisting oncogenic herpesvirus induced by the tumour promoter TPA. Nature 27, 373-375. [Google Scholar]
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