Abstract
BZLF1 repression of transcription from the Epstein-Barr virus BC-R2 promoter (Cp) was shown to require a glucocorticoid response element in cis and glucocorticoids in trans. The mechanism of the repression is indirect and involves up regulation of the cellular c-fos proto-oncogene. Glucocorticoids maintain Epstein-Barr virus latency, and removal of glucocorticoids from the cell culture medium results in activation of the productive cycle. This inverse regulation of the expression of latent and productive cycle genes contributes to the switch between virus latency and the productive cycle. Glucocorticoid control of BC-R2 might also provide a mechanism for EBNA promoter switching during early infection and in development of the restricted latent pattern of gene expression.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
- Bauer G. Induction of Epstein-Barr virus early antigens by corticosteroids: inhibition by TPA and retinoic acid. Int J Cancer. 1983 Mar 15;31(3):291–295. doi: 10.1002/ijc.2910310307. [DOI] [PubMed] [Google Scholar]
- Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
- Bodescot M., Perricaudet M., Farrell P. J. A promoter for the highly spliced EBNA family of RNAs of Epstein-Barr virus. J Virol. 1987 Nov;61(11):3424–3430. doi: 10.1128/jvi.61.11.3424-3430.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buschle M., Brenner M. K., Chen I. S., Drexler H. G., Gignac S. M., Rooney C. M. Transfection and gene expression in normal and malignant primary B lymphocytes. J Immunol Methods. 1990 Oct 4;133(1):77–85. doi: 10.1016/0022-1759(90)90321-l. [DOI] [PubMed] [Google Scholar]
- Danesch U., Gloss B., Schmid W., Schütz G., Schüle R., Renkawitz R. Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements. EMBO J. 1987 Mar;6(3):625–630. doi: 10.1002/j.1460-2075.1987.tb04800.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dietrich J. B., Chasserot-Golaz S., Beck G., Bauer G. Antagonism of glucocorticoid induction of Epstein-Barr virus early antigens by different steroids in Daudi lymphoma cells. J Steroid Biochem. 1986 Jan;24(1):417–421. doi: 10.1016/0022-4731(86)90093-2. [DOI] [PubMed] [Google Scholar]
- Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farrell P. J., Allan G. J., Shanahan F., Vousden K. H., Crook T. p53 is frequently mutated in Burkitt's lymphoma cell lines. EMBO J. 1991 Oct;10(10):2879–2887. doi: 10.1002/j.1460-2075.1991.tb07837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farrell P. J., Rowe D. T., Rooney C. M., Kouzarides T. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J. 1989 Jan;8(1):127–132. doi: 10.1002/j.1460-2075.1989.tb03356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flemington E., Speck S. H. Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol. 1990 Mar;64(3):1227–1232. doi: 10.1128/jvi.64.3.1227-1232.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flemington E., Speck S. H. Epstein-Barr virus BZLF1 trans activator induces the promoter of a cellular cognate gene, c-fos. J Virol. 1990 Sep;64(9):4549–4552. doi: 10.1128/jvi.64.9.4549-4552.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fåhraeus R., Jansson A., Ricksten A., Sjöblom A., Rymo L. Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7390–7394. doi: 10.1073/pnas.87.19.7390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Ham J., Thomson A., Needham M., Webb P., Parker M. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus. Nucleic Acids Res. 1988 Jun 24;16(12):5263–5276. doi: 10.1093/nar/16.12.5263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunt S. P., Pini A., Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature. 1987 Aug 13;328(6131):632–634. doi: 10.1038/328632a0. [DOI] [PubMed] [Google Scholar]
- Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
- Kenney S., Kamine J., Holley-Guthrie E., Lin J. C., Mar E. C., Pagano J. The Epstein-Barr virus (EBV) BZLF1 immediate-early gene product differentially affects latent versus productive EBV promoters. J Virol. 1989 Apr;63(4):1729–1736. doi: 10.1128/jvi.63.4.1729-1736.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kouzarides T., Packham G., Cook A., Farrell P. J. The BZLF1 protein of EBV has a coiled coil dimerisation domain without a heptad leucine repeat but with homology to the C/EBP leucine zipper. Oncogene. 1991 Feb;6(2):195–204. [PubMed] [Google Scholar]
- Kupfer S. R., Summers W. C. Identification of a glucocorticoid-responsive element in Epstein-Barr virus. J Virol. 1990 May;64(5):1984–1990. doi: 10.1128/jvi.64.5.1984-1990.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucibello F. C., Slater E. P., Jooss K. U., Beato M., Müller R. Mutual transrepression of Fos and the glucocorticoid receptor: involvement of a functional domain in Fos which is absent in FosB. EMBO J. 1990 Sep;9(9):2827–2834. doi: 10.1002/j.1460-2075.1990.tb07471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Packham G., Economou A., Rooney C. M., Rowe D. T., Farrell P. J. Structure and function of the Epstein-Barr virus BZLF1 protein. J Virol. 1990 May;64(5):2110–2116. doi: 10.1128/jvi.64.5.2110-2116.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ricksten A., Svensson C., Welinder C., Rymo L. Identification of sequences in Epstein-Barr virus DNA required for the expression of the second Epstein-Barr virus-determined nuclear antigen in COS-1 cells. J Gen Virol. 1987 Sep;68(Pt 9):2407–2418. doi: 10.1099/0022-1317-68-9-2407. [DOI] [PubMed] [Google Scholar]
- Rooney C. M., Rowe D. T., Ragot T., Farrell P. J. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J Virol. 1989 Jul;63(7):3109–3116. doi: 10.1128/jvi.63.7.3109-3116.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowe D. T., Rowe M., Evan G. I., Wallace L. E., Farrell P. J., Rickinson A. B. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells. EMBO J. 1986 Oct;5(10):2599–2607. doi: 10.1002/j.1460-2075.1986.tb04540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Sample J., Hummel M., Braun D., Birkenbach M., Kieff E. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096–5100. doi: 10.1073/pnas.83.14.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuster C., Chasserot-Golaz S., Urier G., Beck G., Sergeant A. Evidence for a functional glucocorticoid responsive element in the Epstein-Barr virus genome. Mol Endocrinol. 1991 Feb;5(2):267–272. doi: 10.1210/mend-5-2-267. [DOI] [PubMed] [Google Scholar]
- Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
- Serfling E. Autoregulation--a common property of eukaryotic transcription factors? Trends Genet. 1989 May;5(5):131–133. doi: 10.1016/0168-9525(89)90049-8. [DOI] [PubMed] [Google Scholar]
- Sinclair A. J., Brimmell M., Shanahan F., Farrell P. J. Pathways of activation of the Epstein-Barr virus productive cycle. J Virol. 1991 May;65(5):2237–2244. doi: 10.1128/jvi.65.5.2237-2244.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Sugden B., Warren N. A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J Virol. 1989 Jun;63(6):2644–2649. doi: 10.1128/jvi.63.6.2644-2649.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sundar S. K., Ablashi D. V., Armstrong G. R., Zipkin M., Faggioni A., Levine P. H. Steroids inhibit tumor promoting agent induced Epstein-Barr virus early antigens in Raji cells. Int J Cancer. 1981 Oct 15;28(4):503–507. doi: 10.1002/ijc.2910280417. [DOI] [PubMed] [Google Scholar]
- Sung N. S., Kenney S., Gutsch D., Pagano J. S. EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus. J Virol. 1991 May;65(5):2164–2169. doi: 10.1128/jvi.65.5.2164-2169.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takada K., Ono Y. Synchronous and sequential activation of latently infected Epstein-Barr virus genomes. J Virol. 1989 Jan;63(1):445–449. doi: 10.1128/jvi.63.1.445-449.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomita M., Chrousos G. P., Brandon D. D., Ben-Or S., Foster C. M., De Vougn L., Taylor S., Loriaux D. L., Lipsett M. B. Glucocorticoid receptors in Epstein-Barr virus-transformed human lymphocytes. Horm Metab Res. 1985 Dec;17(12):674–678. doi: 10.1055/s-2007-1013641. [DOI] [PubMed] [Google Scholar]
- Walls D., Perricaudet M. Novel downstream elements upregulate transcription initiated from an Epstein-Barr virus latent promoter. EMBO J. 1991 Jan;10(1):143–151. doi: 10.1002/j.1460-2075.1991.tb07930.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang F., Tsang S. F., Kurilla M. G., Cohen J. I., Kieff E. Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. J Virol. 1990 Jul;64(7):3407–3416. doi: 10.1128/jvi.64.7.3407-3416.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woisetschlaeger M., Jin X. W., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. H. Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3942–3946. doi: 10.1073/pnas.88.9.3942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
- Young L. S., Lau R., Rowe M., Niedobitek G., Packham G., Shanahan F., Rowe D. T., Greenspan D., Greenspan J. S., Rickinson A. B. Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. J Virol. 1991 Jun;65(6):2868–2874. doi: 10.1128/jvi.65.6.2868-2874.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]
- Zimber-Strobl U., Suentzenich K. O., Laux G., Eick D., Cordier M., Calender A., Billaud M., Lenoir G. M., Bornkamm G. W. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene. J Virol. 1991 Jan;65(1):415–423. doi: 10.1128/jvi.65.1.415-423.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]