Lytic Epstein–Barr virus infection in epithelial cells but not in B-lymphocytes is dependent on Blimp1 Free

Abstract

Epstein–Barr virus (EBV) replicates in superficial differentiated cells of oral hairy leukoplakia (OHL). Differentiation of squamous epithelial cells depends on B-lymphocyte-induced maturation protein 1 (Blimp1). Here we show that expression of the EBV immediate-early protein BZLF1 is restricted to Blimp1-positive epithelial cells in OHL. Luciferase assays revealed Blimp1-dependent induction of the BZLF1 promoter Zp in epithelial cell lines. Expression of ZEB1, a negative regulator of Zp, and of Xbp-1, which mediates the Blimp1 effect on Zp in B-cells, was not affected by enforced Blimp1 expression. Moreover, Xbp-1 protein expression was not detected in differentiated epithelial cells of OHL. Thus, Blimp1 induces BZLF1 expression in epithelial cells independently of ZEB1 and Xbp-1. In contrast to epithelial cells of OHL, BZLF1 expression was also observed in Blimp1-negative lymphoid cells in infectious mononucleosis tonsils, suggesting that EBV replication in B-cells may be induced independently of terminal differentiation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.038661-0
2012-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/5/1059.html?itemId=/content/journal/jgv/10.1099/vir.0.038661-0&mimeType=html&fmt=ahah

References

  1. Al Tabaa Y., Tuaillon E., Jeziorski E., Ouedraogo D. E., Bolloré K., Rubbo P. A., Foulongne V., Rodière M., Vendrell J. P. 2011; B-cell polyclonal activation and Epstein–Barr viral abortive lytic cycle are two key features in acute infectious mononucleosis. J Clin Virol 52:33–37 [View Article][PubMed]
    [Google Scholar]
  2. Bhende P. M., Dickerson S. J., Sun X., Feng W. H., Kenney S. C. 2007; X-box-binding protein 1 activates lytic Epstein–Barr virus gene expression in combination with protein kinase D. J Virol 81:7363–7370 [View Article][PubMed]
    [Google Scholar]
  3. Binné U. K., Amon W., Farrell P. J. 2002; Promoter sequences required for reactivation of Epstein–Barr virus from latency. J Virol 76:10282–10289 [View Article][PubMed]
    [Google Scholar]
  4. Buettner M., Greiner A., Avramidou A., Jäck H. M., Niedobitek G. 2005; Evidence of abortive plasma cell differentiation in Hodgkin and Reed–Sternberg cells of classical Hodgkin lymphoma. Hematol Oncol 23:127–132 [View Article][PubMed]
    [Google Scholar]
  5. Chang D. H., Cattoretti G., Calame K. L. 2002; The dynamic expression pattern of B lymphocyte induced maturation protein-1 (Blimp-1) during mouse embryonic development. Mech Dev 117:305–309 [View Article][PubMed]
    [Google Scholar]
  6. Crawford D. H., Ando I. 1986; EB virus induction is associated with B-cell maturation. Immunology 59:405–409[PubMed]
    [Google Scholar]
  7. Ellis A. L., Wang Z., Yu X., Mertz J. E. 2010; Either ZEB1 or ZEB2/SIP1 can play a central role in regulating the Epstein–Barr virus latent-lytic switch in a cell-type-specific manner. J Virol 84:6139–6152 [View Article][PubMed]
    [Google Scholar]
  8. Frangou P., Buettner M., Niedobitek G. 2005; Epstein–Barr virus (EBV) infection in epithelial cells in vivo: rare detection of EBV replication in tongue mucosa but not in salivary glands. J Infect Dis 191:238–242 [View Article][PubMed]
    [Google Scholar]
  9. Greenspan J. S., Greenspan D., Lennette 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. N Engl J Med 313:1564–1571 [View Article][PubMed]
    [Google Scholar]
  10. Herrmann K., Frangou P., Middeldorp J., Niedobitek G. 2002; Epstein–Barr virus replication in tongue epithelial cells. J Gen Virol 83:2995–2998[PubMed]
    [Google Scholar]
  11. Karimi L., Crawford D. H., Speck S., Nicholson L. J. 1995; Identification of an epithelial cell differentiation responsive region within the BZLF1 promoter of the Epstein–Barr virus. J Gen Virol 76:759–765 [View Article][PubMed]
    [Google Scholar]
  12. Lagenaur L. A., Palefsky J. M. 1999; Regulation of Epstein–Barr virus promoters in oral epithelial cells and lymphocytes. J Virol 73:6566–6572[PubMed]
    [Google Scholar]
  13. Laichalk L. L., Thorley-Lawson D. A. 2005; Terminal differentiation into plasma cells initiates the replicative cycle of Epstein–Barr virus in vivo. J Virol 79:1296–1307 [View Article][PubMed]
    [Google Scholar]
  14. Lin K. I., Angelin-Duclos C., Kuo T. C., Calame K. 2002; Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells. Mol Cell Biol 22:4771–4780 [View Article][PubMed]
    [Google Scholar]
  15. Magnúsdóttir E., Kalachikov S., Mizukoshi K., Savitsky D., Ishida-Yamamoto A., Panteleyev A. A., Calame K. 2007; Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1. Proc Natl Acad Sci U S A 104:14988–14993 [View Article][PubMed]
    [Google Scholar]
  16. Miller G. 1990; The switch between latency and replication of Epstein–Barr virus. J Infect Dis 161:833–844 [View Article][PubMed]
    [Google Scholar]
  17. Montalvo E. A., Cottam M., Hill S., Wang Y. J. 1995; YY1 binds to and regulates cis-acting negative elements in the Epstein–Barr virus BZLF1 promoter. J Virol 69:4158–4165[PubMed]
    [Google Scholar]
  18. Murray P. G., Niedobitek G., Kremmer E., Grässer F., Reynolds G. M., Cruchley A., Williams D. M., Müller-Lantzsch N., Young L. S. 1996; In situ detection of the Epstein–Barr virus-encoded nuclear antigen 1 in oral hairy leukoplakia and virus-associated carcinomas. J Pathol 178:44–47 [View Article][PubMed]
    [Google Scholar]
  19. Niedobitek G., Young L. S. 1994; Epstein–Barr virus persistence and virus-associated tumours. Lancet 343:333–335 [View Article][PubMed]
    [Google Scholar]
  20. Niedobitek G., Young L. S., Lau R., Brooks L., Greenspan D., Greenspan J. S., Rickinson A. B. 1991; Epstein–Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol 72:3035–3046 [View Article][PubMed]
    [Google Scholar]
  21. Niedobitek G., Agathanggelou A., Herbst H., Whitehead L., Wright D. H., Young L. S. 1997; Epstein–Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells. J Pathol 182:151–159 [View Article][PubMed]
    [Google Scholar]
  22. Rabanus J. P., Greenspan D., Petersen V., Leser U., Wolf H., Greenspan J. S. 1991; Subcellular distribution and life cycle of Epstein–Barr virus in keratinocytes of oral hairy leukoplakia. Am J Pathol 139:185–197[PubMed]
    [Google Scholar]
  23. 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. J Virol 63:3109–3116[PubMed]
    [Google Scholar]
  24. Shannon-Lowe C., Adland E., Bell A. I., Delecluse H. J., Rickinson A. B., Rowe M. 2009; Features distinguishing Epstein–Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J Virol 83:7749–7760 [View Article][PubMed]
    [Google Scholar]
  25. Shapiro-Shelef M., Lin K. I., McHeyzer-Williams L. J., Liao J., McHeyzer-Williams M. G., Calame K. 2003; Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19:607–620 [View Article][PubMed]
    [Google Scholar]
  26. Sun C. C., Thorley-Lawson D. A. 2007; Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein–Barr virus BZLF1 promoter. J Virol 81:13566–13577 [View Article][PubMed]
    [Google Scholar]
  27. Thomas C., Dankesreiter A., Wolf H., Schwarzmann F. 2003; The BZLF1 promoter of Epstein–Barr virus is controlled by E box-/HI-motif-binding factors during virus latency. J Gen Virol 84:959–964 [View Article][PubMed]
    [Google Scholar]
  28. Young L. S., Lau R., Rowe M., Niedobitek G., Packham G., Shanahan F., Rowe D. T., Greenspan D., Greenspan J. S.other authors 1991; Differentiation-associated expression of the Epstein–Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. J Virol 65:2868–2874[PubMed]
    [Google Scholar]
  29. Yu X., Wang Z., Mertz J. E. 2007; ZEB1 regulates the latent-lytic switch in infection by Epstein–Barr virus. PLoS Pathog 3:e194 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.038661-0
Loading
/content/journal/jgv/10.1099/vir.0.038661-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed