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Journal of Virology, July 2007, p. 7598-7607, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02435-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Truncated Form of the Epstein-Barr Virus Protein EBNA-LP Protects against Caspase-Dependent Apoptosis by Inhibiting Protein Phosphatase 2A{triangledown}

Julie Garibal,1 Émilie Hollville,1 Andrew I. Bell,2 Gemma L. Kelly,2 Benjamin Renouf,1 Yasushi Kawaguchi,3 Alan B. Rickinson,2 and Joëlle Wiels1*

UMR 8126 CNRS, University Paris-Sud, Institut Gustave Roussy, 94805 Villejuif cedex, France,1 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom,2 Department of Infectious Disease Control, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan3

Received 6 November 2006/ Accepted 3 May 2007

The Epstein-Barr virus (EBV)-encoded leader protein, EBNA-LP, strongly activates the EBNA2-mediated transcriptional activation of cellular and viral genes and is therefore important for EBV-induced B-cell transformation. However, a truncated form of EBNA-LP is produced in cells infected with variant EBV strains lacking EBNA2 due to a genetic deletion. The function of this truncated form is unknown. We show here that some Burkitt's lymphoma cells harboring defective EBV strains are specifically resistant to the caspase-dependent apoptosis induced by verotoxin 1 (VT-1) or staurosporine. These cells produced low-molecular-weight Y1Y2-truncated isoforms of EBNA-LP, which were partly localized in the cytoplasm. The transfection of sensitive cells with constructs encoding truncated EBNA-LP isoforms, but not full-length EBNA-LP, induced resistance to caspase-mediated apoptosis. Furthermore, VT-1 induced protein phosphatase 2A (PP2A) activation in sensitive cells but not in resistant cells, in which the truncated EBNA-LP interacted with this protein. Thus, the resistance to apoptosis observed in cells harboring defective EBV strains most probably results from the inactivation of PP2A via interactions with low-molecular-weight Y1Y2-truncated EBNA-LP isoforms.

* Corresponding author. Mailing address: CNRS UMR 8126, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif cedex, France. Phone: 33 1 42 11 47 40. Fax: 33 1 42 11 54 94. E-mail: wiels{at}igr.fr

{triangledown} Published ahead of print on 9 May 2007.

Journal of Virology, July 2007, p. 7598-7607, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02435-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ling, P. D., Tan, J., Peng, R. (2009). Nuclear-Cytoplasmic Shuttling Is Not Required for the Epstein-Barr Virus EBNA-LP Transcriptional Coactivation Function. J. Virol. 83: 7109-7116 [Abstract] [Full Text]  
  • Lucchesi, W., Brady, G., Dittrich-Breiholz, O., Kracht, M., Russ, R., Farrell, P. J. (2008). Differential Gene Regulation by Epstein-Barr Virus Type 1 and Type 2 EBNA2. J. Virol. 82: 7456-7466 [Abstract] [Full Text]  


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