1887

Abstract

The hallmark of Epstein—Barr virus (EBV) infection is the establishment of a viral genome transcription pattern called latency. The EBV BZLF1 gene product EB1 (also known as ZEBRA or Zta) is a transcription factor which is essential for the switch from latency to the lytic cycle. It has been proposed that latency is maintained () by the inhibition of EB1 translation via antisense hybridization of EBNA1 and EB1 hnRNAs, or () by the inactivation of the EB1 activating function via the direct interaction of EB1 with ReIA, the retinoic acid receptor and p53, or via the titration of EB1 in RAZ:EB1 inactive heterodimers that are unable to bind to DNA. RAZ, a fusion protein which contains the EB1 C-terminal dimerization and DNA-binding domains fused to the N-terminal 86 amino acids of the EBV BRLF1 gene product R, has been described as a -dominant negative regulator of EB1-activated transcription. We demonstrate here that although RAZ efficiently represses EB1-mediated transcriptional activation, the amount of RAZ protein expressed is incompatible with repression through the titration of EB1 in inactive EB1:RAZ heterodimers. Furthermore, we also demonstrate that RAZ efficiently represses transcription activated by an EB1 mutant carrying the GCN4 homodimerization domain (EB1), despite the inability of RAZ and EB1 to form stable heterodimers.

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1996-07-01
2024-03-28
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References

  1. Buisson M., Manet E., Trescol-Biemont M.-C., Gruffat H., Durand B., Sergeant A. 1989; The Epstein–Barr virus (EBV) early protein EB2 is a posttranscriptional activator expressed under the control of EBV transcription factors EB1 and R. Journal of Virology 63:5276–5284
    [Google Scholar]
  2. Chang Y., Dong D., Hayward G., Hayward S. 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. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillie J., Sergeant A. 1986; Both Epstein–Barr virus (EBV)-encoded transacting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO Journal 5:3243–3249
    [Google Scholar]
  4. Cho M.-S., Tran V.-M. 1993; A concatenated form of Epstein–Barr viral DNA in lymphoblastoid cell lines induced by transfection with BZLF1. Virology 194:838–842
    [Google Scholar]
  5. 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
    [Google Scholar]
  6. Countryman J. K., Jenson H., Grogan E., Miller G. 1989; A 2.7-kb rearranged DNA fragment from Epstein–Barr virus capable of disruption of latency. Cancer Cells 4:517–523
    [Google Scholar]
  7. Farrell P. J., Rowe D. T., Rooney C. M., Kouzarides T. 1989; Epstein–Barr virus BZLFI transactivator specifically binds to a consensus AP-1 site and is related to cFos. EMBO Journal 8:127–132
    [Google Scholar]
  8. Fixman E. D., Hayward G. S., Hayward S. D. 1995; Replication of Epstein–Barr virus oriLyt: lack of a dedicated virally encoded originbinding protein and dependence on Zta in cotransfection assays. Journal of Virology 69:2998–3006
    [Google Scholar]
  9. Flemington E., Speck S. H. 1990a; Evidence for coiled-coil dimer formation by an Epstein–Barr virus transactivator that lacks a heptad repeat of leucine residues. Proceedings of the National Academy of Sciences, USA 87:9459–9463
    [Google Scholar]
  10. Flemington E., Speck S. H. 1990b; Autoregulation of Epstein–Barr virus putative lytic cycle switch gene BZLF1. Journal of Virology 64:1227–1232
    [Google Scholar]
  11. Furnari F., Zacny V., Quilivan B., Kenney S., Pagano J. 1994; RAZ, an Epstein–Barr virus transdominant repressor that modulates the viral reactivation mechanism. Journal of Virology 68:1827–1836
    [Google Scholar]
  12. Giot J.-F., Mikaelian I., Buisson M., Manet E., Joab I., Nicolas J.-C., Sergeant A. 1991; Transcriptional interference between the EBV transcription factors EB1 and R: both DNA–binding and activation domains of EB1 are required. Nucleic Acids Research 19:1251–1258
    [Google Scholar]
  13. Gorman C., Moffat L., Howard B. 1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  14. 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
    [Google Scholar]
  15. Gutsch D. E., Holley-Guthrie E. A., Zhang Q., Stein B., Blanar M. A., Baldwin A. S., Kenney S. C. 1994; The bZIP transactivator of Epstein–Barr virus, BZLF1, functionally and physically interacts with the p65 subunit of NF-k B. Molecular and Cellular Biology 14:1939–1948
    [Google Scholar]
  16. 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]
  17. Kelleher C., Paterson R., Dreyfus D., Streib J., Xu J., Takase K., Jones J., Gelfand E. 1995; Epstein–Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-I and its repressor RAZ. Virology 208:685–695
    [Google Scholar]
  18. Kouzarides T., Packhman G., Cook A., Farrell P. 1991; The BZLF1 protein of EBV has a coiled dimerisation domain without a heptad repeat but with homology to the C/EBP leucine zipper. Oncogene 6:195–204
    [Google Scholar]
  19. Liebowitz D., Kieff E. 1993; Epstein–Barr virus. In The Human Herpesviruses pp 107–172 Edited by Roizman B., Whitley R. J., Lopez C. New York: Raven Press;
    [Google Scholar]
  20. Manet E., Gruffat H., Trescol-Biemont M.-C., Moreno N., Chambard P., Giot J.-F., Sergeant A. 1989; Epstein–Barr bicistronic mRNAs generated by facultative splicing code for two transcriptional transactivators. EMBO Journal 8:1819–1826
    [Google Scholar]
  21. Mikaelian I., Drouet E., Marechai V., Denoyel G., Nicolas J.-C., Sergeant A. 1993a; The DNA-binding domain of two bZIP transcription factors, the Epstein–Barr virus switch gene product EB1 and Jun, is a bipartite nuclear targeting sequence. Journal of Virology 67:734–742
    [Google Scholar]
  22. Mikaelian I., Manet E., Sergeant A. 1993b; The bZIP motif of the Epstein–Barr virus (EBV) transcription factor EB1 mediates a direct interaction with TBP. Compte Rendu de I’Academie des Sciences 316:1424–1432
    [Google Scholar]
  23. Prang N., Wolf H., Schwarzmann F. 1995; Epstein–Barr virus lytic replication is controlled by posttranscriptional negative regulation of BZLF1. Journal of Virology 69:2644–2648
    [Google Scholar]
  24. Rooney C., Rowe D., Ragot T., Farrell P. 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]
  25. Schepers A., Pich D., Hammerschmidt W. 1993; Transcription factor with homology to the AP–I family links RNA transcription and DNA replication in the lytic cycle of Epstein–Barr virus. EMBO Journal 12:3921–3929
    [Google Scholar]
  26. Sista N. D., Pagano J. S., Liao W., Kenney S. 1993; Retinoic acid is a negative regulator of the Epstein–Barr virus protein (BZLF1) that mediates disruption of latent infection. Proceedings of the National Academy of Sciences, USA 90:3894–3898
    [Google Scholar]
  27. Sista N. D., Barry C., Sampson K., Pagano J. 1995; Physical and functional interaction of the Epstein–Barr virus BZLFI transactivator with the retinoic acid receptors RARα and RXRα. Nucleic Acids Research 23:1729–1736
    [Google Scholar]
  28. Takada K., Shimizu N., Sakuma S., Ono Y. 1986; Transactivation of the latent Epstein–Barr virus (EBV) genome after transfection of the EBV DNA fragment. Journal of Virology 57:1016–1022
    [Google Scholar]
  29. 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]
  30. Zhang Q., Gutsch D., Kenney S. 1994; Functional and physical interaction between p53 and BZLF1: implications for Epstein–Barr virus latency. Molecular and Cellular Biology 14:1929–1938
    [Google Scholar]
  31. zur Hausen H., O’Neill F. J., Freese U.K., Hecker E. 1978; Persisting oncogenic herpesvirus induced by the tumor promoter TP A. Nature 272:373–375
    [Google Scholar]
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