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Journal of Virology, March 2001, p. 2033-2040, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2033-2040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activated Notch1 Can Transiently Substitute for EBNA2 in the Maintenance of Proliferation of LMP1-Expressing Immortalized B Cells

Heike Höfelmayr, Lothar J. Strobl,dagger Gabriele Marschall, Georg W. Bornkamm, and Ursula Zimber-Strobl*

Institute for Clinical Molecular Biology and Tumor Genetics, GSF National Research Center of Environment and Health, D-81377 Munich, Germany

Received 24 August 2000/Accepted 1 December 2000

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for immortalization of human B cells by EBV. EBNA2 and activated Notch transactivate genes by interacting with the cellular transcription factor RBP-Jkappa /CBF1. Therefore, EBNA2 can be regarded as a functional homologue of activated Notch. We have shown previously that the intracellular domain of Notch1 (Notch1-IC) is able to transactivate EBNA2-regulated viral promoters and to induce phenotypic changes in B cells similar to those caused by EBNA2. Here we investigated whether Notch1-IC can substitute for EBNA2 in the maintenance of B-cell proliferation. Using an EBV-immortalized lymphoblastoid cell line in which EBNA2 function can be regulated by estrogen, we demonstrate that murine Notch1-IC, in the absence of functional EBNA2, is unable to maintain LMP1 expression and to maintain cell proliferation. However, in a lymphoblastoid cell line expressing LMP1 independently of EBNA2, murine Notch1-IC can transiently maintain proliferation after EBNA2 inactivation. After 4 days, cell numbers do not increase further, and cells in the G2 phase of the cell cycle start to die. In contrast to EBNA2, murine Notch1-IC is unable to upregulate the expression of the c-myc gene in these cells.

* Corresponding author. Present address: Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany. Phone: 49-221-470-3416. Fax: 49-221-470-5185. E-mail: u.strobl{at}uni-koeln.de

dagger Present address: Institute for Genetics, University of Cologne, D-50931 Cologne, Germany.

Journal of Virology, March 2001, p. 2033-2040, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2033-2040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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