Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Aug;65(8):4101–4106. doi: 10.1128/jvi.65.8.4101-4106.1991

Epstein-Barr virus nuclear protein 2 transactivates a cis-acting CD23 DNA element.

F Wang 1, H Kikutani 1, S F Tsang 1, T Kishimoto 1, E Kieff 1
PMCID: PMC248842  PMID: 1649318

Abstract

Epstein-Barr virus (EBV) nuclear protein 2 (EBNA-2) is essential for B-lymphocyte growth transformation. EBNA-2 upregulates mRNAs encoding CD23, a B-lymphocyte surface protein closely associated with EBV-induced growth transformation. To further investigate this EBNA-2 effect, we searched in the genomic DNA spanning the type a and type b CD23 mRNA start sites for a cis-acting fragment that would render a promoter transactivatable by EBNA-2. An 800-bp CD23 DNA fragment (-335 to +465 relative to the type a CD23 mRNA start site) conferred EBNA-2 responsiveness to the herpes simplex virus thymidine kinase (TK) promoter when transfected into EBV-negative B-lymphoma cells. Deletional analysis identified a -275/-89 subfragment that was EBNA-2 responsive when cloned in either orientation and at variable distances upstream of the heterologous promoter. EBNA-2 and the cis-acting CD23 element increased TK-promoted mRNA and did not alter the herpes simplex virus TK promoter transcription start site. As expected, a type a CD23 promoter (-335/+80) which contained the EBNA-2-responsive element was transactivated by EBNA-2. As in EBV infection and stable EBNA-2 transfection, the CD23 DNA element in cis with heterologous or homologous promoters was less responsive to type 2 than to type 1 EBNA-2, whereas the EBNA-2-responsive DNA fragment from the EBV latent membrane protein 1 promoter was more responsive to the type 2 EBNA-2. These experiments delineate a 186-bp, EBNA-2-responsive cell DNA fragment and provide firm evidence that EBNA-2 transactivates transcription of cell genes. The greater type 1 versus type 2 EBNA-2 responsiveness of the CD23 promoter and the lack of a similar effect on the latent membrane protein 1 promoter is consistent with the hypothesis that greater cell gene transactivation by type 1 EBNA-2 is the basis for the more efficient growth-transforming properties of type 1 EBV.

Full text

PDF
4101

Images in this article

4103Image
on p.4103
4103Image
on p.4103
4103Image
on p.4103
4104Image
on p.4104

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbot S. D., Rowe M., Cadwallader K., Ricksten A., Gordon J., Wang F., Rymo L., Rickinson A. B. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. J Virol. 1990 May;64(5):2126–2134. doi: 10.1128/jvi.64.5.2126-2134.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. An G., Hidaka K., Siminovitch L. Expression of bacterial beta-galactosidase in animal cells. Mol Cell Biol. 1982 Dec;2(12):1628–1632. doi: 10.1128/mcb.2.12.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azim T., Crawford D. H. Lymphocytes activated by the Epstein-Barr virus to produce immunoglobulin do not express CD23 or become immortalized. Int J Cancer. 1988 Jul 15;42(1):23–28. doi: 10.1002/ijc.2910420106. [DOI] [PubMed] [Google Scholar]
  4. Banchereau J., de Paoli P., Vallé A., Garcia E., Rousset F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70–72. doi: 10.1126/science.1702555. [DOI] [PubMed] [Google Scholar]
  5. Calender A., Billaud M., Aubry J. P., Banchereau J., Vuillaume M., Lenoir G. M. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060–8064. doi: 10.1073/pnas.84.22.8060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen J. I., Wang F., Kieff E. Epstein-Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation. J Virol. 1991 May;65(5):2545–2554. doi: 10.1128/jvi.65.5.2545-2554.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen J. I., Wang F., Mannick J., Kieff E. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558–9562. doi: 10.1073/pnas.86.23.9558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Hammerschmidt W., Sugden B. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes. Nature. 1989 Aug 3;340(6232):393–397. doi: 10.1038/340393a0. [DOI] [PubMed] [Google Scholar]
  10. Kikutani H., Suemura M., Owaki H., Nakamura H., Sato R., Yamasaki K., Barsumian E. L., Hardy R. R., Kishimoto T. Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. J Exp Med. 1986 Nov 1;164(5):1455–1469. doi: 10.1084/jem.164.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kintner C., Sugden B. Identification of antigenic determinants unique to the surfaces of cells transformed by Epstein-Barr virus. Nature. 1981 Dec 3;294(5840):458–460. doi: 10.1038/294458a0. [DOI] [PubMed] [Google Scholar]
  12. Knutson J. C. The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization. J Virol. 1990 Jun;64(6):2530–2536. doi: 10.1128/jvi.64.6.2530-2536.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Rickinson A. B., Young L. S., Rowe M. Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J Virol. 1987 May;61(5):1310–1317. doi: 10.1128/jvi.61.5.1310-1317.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Suter U., Texido G., Hofstetter H. Expression of human lymphocyte IgE receptor (Fc epsilon RII/CD23). Identification of the Fc epsilon RIIa promoter and its functional analysis in B lymphocytes. J Immunol. 1989 Nov 1;143(9):3087–3092. [PubMed] [Google Scholar]
  17. Thorley-Lawson D. A., Mann K. P. Early events in Epstein-Barr virus infection provide a model for B cell activation. J Exp Med. 1985 Jul 1;162(1):45–59. doi: 10.1084/jem.162.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  19. Wang F., Gregory C. D., Rowe M., Rickinson A. B., Wang D., Birkenbach M., Kikutani H., Kishimoto T., Kieff E. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. Proc Natl Acad Sci U S A. 1987 May;84(10):3452–3456. doi: 10.1073/pnas.84.10.3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wang F., Gregory C., Sample C., Rowe M., Liebowitz D., Murray R., Rickinson A., Kieff E. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol. 1990 May;64(5):2309–2318. doi: 10.1128/jvi.64.5.2309-2318.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Yokota A., Kikutani H., Tanaka T., Sato R., Barsumian E. L., Suemura M., Kishimoto T. Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Cell. 1988 Nov 18;55(4):611–618. doi: 10.1016/0092-8674(88)90219-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES