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Journal of Virology, October 2006, p. 9761-9771, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00665-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cellular Target Genes of Epstein-Barr Virus Nuclear Antigen 2

Sabine Maier,1 Gabriele Staffler,1 Andrea Hartmann,1 Julia Höck,1 Karen Henning,2 Kristina Grabusic,1 Reinhard Mailhammer,1 Reinhard Hoffmann,3 Matthias Wilmanns,2 Roland Lang,4 Jörg Mages,4 and Bettina Kempkes1*

GSF-National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Munich, Germany,1 EMBL-Hamburg, Hamburg, Germany,2 Department of Bacteriology, Max von Pettenkofer Institute,3 Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany4

Received 3 April 2006/ Accepted 20 July 2006

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the EBV-driven B-cell growth transformation process. By activating an array of viral and cellular target genes, EBNA-2 initiates a cascade of events which ultimately cause cell cycle entry and the proliferation of the infected B cell. In order to identify cellular target genes that respond to EBNA-2 in the absence of other viral factors, we have performed a comprehensive search for EBNA-2 target genes in two EBV-negative B-cell lines. This screen identified 311 EBNA-2-induced and 239 EBNA-2-repressed genes that were significantly regulated in either one or both cell lines. The activation of most of these genes had not previously been attributed to EBNA-2 function and will be relevant for the identification of EBNA-2-specific contributions to EBV-associated malignancies. The diverse spectrum of EBNA-2 target genes described in this study reflects the broad spectrum of EBNA-2 functions involved in virus-host interactions, including cell signaling molecules, adapters, genes involved in cell cycle regulation, and chemokines.

* Corresponding author. Mailing address: Institute of Clinical Molecular Biology, Marchioninistr. 25, D-81377 Munich, Germany. Phone: 49-89-7099354. Fax: 49-89-7099361. E-mail: kempkes{at}gsf.de.

Journal of Virology, October 2006, p. 9761-9771, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00665-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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