1887

Abstract

Epstein-Barr virus (EBV) replicates in a latent or a lytic way in the infected organism, depending on the type and level of differentiation of the host cell. The switch between latency and lytic replication was previously shown, for Burkitt’s lymphoma cell lines, to depend on the viral BZLF1 gene product. Protein-DNA assays were used to identify the cis-acting elements that represent the link between regulating signal transduction pathways and the viral cascade of gene expression. Specific binding of proteins to several sites of the BZLF1 promoter during latency was shown. Induction of the lytic cycle by stimulation with 12--tetradecanoyl- phorbol 13-acetate abolished the binding of these proteins to the distal promoter (positions −227 to −551), suggesting a functional role for the down- regulation of promoter activity during latency. Computer analysis identified a multiply repeated sequence motif, HI, in this region and exonuclease III footprints confirmed that these sites act as specific protein recognition sites. Using a set of reporter plasmids we were able to demonstrate a negative regulatory effect of the HI motif in some B lymphoid cell lines, in contrast to epithelial HeLa cells. The HI silencer elements are different from other silencer elements described so far in respect of their sequence and protein-binding pattern during the activation of BZLF1.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-8-1999
1994-08-01
2024-12-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/8/JV0750081999.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-8-1999&mimeType=html&fmt=ahah

References

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell G. C., Seguin C., Tuffnell P. S., Barrell B. G. 1984; DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature; London: 310207–211
    [Google Scholar]
  2. Becker J., Leser U., Marschall M., Langford A., Jilg W., Reichart P., Gelderblom H., Wolf H. 1991; Expression of proteins encoded by Epstein-Barr virus trans-activator genes depends on the differentiation of epithelial cells in oral hairy leukoplakia. Proceedings of the National Academy of Sciences, U.S.A 88:8332–8336
    [Google Scholar]
  3. Bogedain C., Alliger P., Schwarzmann F., Marschall M., Wolf H., Jilg W. 1994; Different activation of Epstein-Barr virus immediate early- and late-genes in Burkitt-lymphoma cells and lymphoblastoid cell lines. Journal of Virology 68:1200–1203
    [Google Scholar]
  4. Chavrier P., Gruffat H., Cjevallier-Greco A., Buisson M., Sergeant A. 1989; The Epstein-Barr virus (EBV) early promoter DR contains a cis-acting element responsive to the EBV transactivatorEB1 and an enhancer with constitutive and inducible activities. Journal of Virology 63:607–614
    [Google Scholar]
  5. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillier 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]
  6. Chevallier-Greco A., Gruffat H., Manet E., Calender A., Sergeant A. 1989; The Epstein-Barr virus (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]
  7. Countryman J., Jenson H., Seibl R., Wolf H., Miller G. 1987; Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency. Journal of Virology 61:3672–3679
    [Google Scholar]
  8. Cox M. A., Leahy J., Hardwick J. M. 1990; An enhancer within the divergent promoter of Epstein-Barr virus responds synergisti- cally to the R and Z transactivators. Journal of Virology 64:313–321
    [Google Scholar]
  9. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Research 12:387–395
    [Google Scholar]
  10. Dignam J. D., Lebovitz R. M., Roeder E. G. 1983; Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Research 11:1475–1489
    [Google Scholar]
  11. Flemington E., Speck S. 1990a; Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. Journal of Virology 64:1217–1226
    [Google Scholar]
  12. Flemington E., Speck S. 1990b; Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. Journal of Virology 64:1227–1232
    [Google Scholar]
  13. Greenspan J. S., Greenspan D., Lenette E. T., Abrams D. I., Conant M. A., Petersen V., Freese U. K. 1985; Replication OF Epstein-Barr virus within the epithelial cells of oral ‘hairy’ leukoplakia, an AIDS associated lesion. New England Journal of Medicine 313:1564–1571
    [Google Scholar]
  14. Gualberto A., LePage D., Pons G., Mader S. L., Park K., Atchison M. L., Walsh K. 1992; Functional antagonism between YY1 and the serum response factor. Molecular and Cellular Biology 12:4209–4214
    [Google Scholar]
  15. Hennighausen L., Lubon H. 1987; Interaction of protein with DNA in vitro. Methods in Enzymology 152:721–735
    [Google Scholar]
  16. Higuchi R. 1990; Recombinant PCR. In PCR Protocols: A Guide to Methods and Applications pp. 177–183 Innis M. A., Gelfand D. H., Sninski J. J., White T. J. Edited by San Diego: Academic Press;
    [Google Scholar]
  17. Kenney S., Holley-Guthrie E., Mar E. C., Smith M. 1989a; The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators. Journal of Virology 63:3878–3883
    [Google Scholar]
  18. Kenney S., Kamine J., Holley-Guthrie E., Lin J.-C., Pagano J. 1989b; The Epstein-Barr virus (EBV) BZLF1 immediate early gene product differentially affects latent versus productive EBV promoters. Journal of Virology 63:1729–1736
    [Google Scholar]
  19. Lieberman P. M., Hardwick J. M., Sample J., Hayward G. S., Hayward S. D. 1990; The Zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus infected lymphocytes binds both API and ZRE sites in target promoter and enhancer regions. Journal of Virology 64:1143–1155
    [Google Scholar]
  20. Marschall M., Motz M., Leser U., Schwarzmann F., Oker B., Wolf H. 1989; Hepatitis B virus surface antigen as a reporter of promoter activity. Gene 81:109–117
    [Google Scholar]
  21. Marschall M., Schwarzmann F., Leser U., Oker B., Alliger P., Mairhofer H., Wolf H. 1991; The BT′LF4 trans-activator of Epstein-Barr virus is modulated by type and differentiation of the host cell. Virology 181:172–179
    [Google Scholar]
  22. Montalvo E. A., Shi Y., Shenk T. E., Levine A. J. 1991; Negative regulation of the BZLF1 promoter of Epstein-Barr virus. Journal of Virology 65:3647–3655
    [Google Scholar]
  23. Rauscher F. J.III Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohman D., Tuan R. 1988; Fos-associated protein p39 is the product of the jun proto-oncogene. Science 240:1010–1016
    [Google Scholar]
  24. 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]
  25. Seto E., Shi Y., Shenk T. 1991; YY1 is an initiator sequencebinding protein that directs and activates transcription in vitro. Nature; London: 354241–245
    [Google Scholar]
  26. Sixbey J. W., Lemon S. M., Pagano J. S. 1986; A second site for Epstein-Barr virus shedding: the uterine cervix. Lancet ii:1122–1124
    [Google Scholar]
  27. Skare J., Strominger J. L. 1980; Cloning and mapping of BamHI endonuclease fragments of DNA from the transforming B95-8 strain of Epstein-Barr virus. Proceedings of the National Academy of Sciences, U.S.A 77:3860–3864
    [Google Scholar]
  28. Treisman R. 1986; Identification of a protein-binding site that mediates transcriptional response to the c-fos gene to serum factors. Cell 46:567–574
    [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 AP1 binding sites. EMBO Journal 8:1447–1453
    [Google Scholar]
  30. Vogel K., Hörz W., Hinnen A. 1989; The two positively acting regulatory proteins PHO2 and PHO4 physically interact with PHO5 upstream activation regions. Molecular and Cellular Biology 9:2050–2057
    [Google Scholar]
  31. Wolf H., Haus M., Wilmes E. 1984; Persistence of Epstein-Barr virus in the parotid gland. Journal of Virology 51:795–798
    [Google Scholar]
  32. Young L. S., Lau R., Rowe M., Niedobitek G., Packham G., Shanahan F., Rowe D. T., Greenspan D., Rickinson A. B., Farrell P. J. 1991; Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. Journal of Virology 65:2868–2874
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-75-8-1999
Loading
/content/journal/jgv/10.1099/0022-1317-75-8-1999
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error