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Journal of Virology, August 2006, p. 7382-7393, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02052-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Autoactivation of the Epstein-Barr Virus Oncogenic Protein LMP1 during Type II Latency through Opposite Roles of the NF-{kappa}B and JNK Signaling Pathways

Gautier Goormachtigh,1 Tan-Sothéa Ouk,1 Alexandra Mougel,1 Denis Tranchand-Bunel,1 Eric Masy,2 Christophe Le Clorennec,3 Jean Feuillard,3 Georg W. Bornkamm,4 Claude Auriault,1 Evelyne Manet,5 Véronique Fafeur,6 Eric Adriaenssens,1,7 and Jean Coll1*

CNRS UMR 8527, Institut de Biologie de Lille (IBL), Lille, France,1 Service de Biologie Clinique, Centre Hospitalier, Valenciennes, France,2 CNRS UMR 6101 and Laboratoire d'Hématologie, Faculté de Médecine, Université de Limoges, CHU Dupuytren, Limoges, France,3 GSF-Institute of Clinical Molecular Biology and Tumor Genetics, Munich, Germany,4 INSERM U412, Ecole Normale Supérieure de Lyon, Lyon, France,5 CNRS UMR 8117, Institut de Biologie de Lille (IBL), Lille, France,6 ERI-8 INSERM, UPRES-EA-1033, Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France7

Received 27 September 2005/ Accepted 16 May 2006

Epstein-Barr virus (EBV) is associated with several human malignancies where it expresses limited subsets of latent proteins. Of the latent proteins, latent membrane protein 1 (LMP1) is a potent transforming protein that constitutively induces multiple cell signaling pathways and contributes to EBV-associated oncogenesis. Regulation of LMP1 expression has been extensively described during the type III latency of EBV. Nevertheless, in the majority of EBV-associated tumors, the virus is commonly found to display a type II latency program in which it is still unknown which viral or cellular protein is really involved in maintaining LMP1 expression. Here, we demonstrate that LMP1 activates its own promoter pLMP1 through the JNK signaling pathway emerging from the TES2 domain. Our results also reveal that this activation is tightly controlled by LMP1, since pLMP1 is inhibited by LMP1-activated NF-{kappa}B signaling pathway. By using our physiological models of EBV-infected cells displaying type II latency as well as lymphoblastoid cell lines expressing a type III latency, we also demonstrate that this balanced autoregulation of LMP1 is shared by both latency programs. Finally, we show that this autoactivation is the most important mechanism to maintain LMP1 expression during the type II latency program of EBV.

* Corresponding author. Mailing address: CNRS UMR 8527, Institut de Biologie de Lille (IBL), 1 rue du Pr. Calmette, 59021 Lille Cedex, France. Phone: 33-320871234. Fax: 33-320871233. E-mail: jean.coll{at}ibl.fr.

Journal of Virology, August 2006, p. 7382-7393, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02052-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Demetriades, C., Mosialos, G. (2009). The LMP1 Promoter Can Be Transactivated Directly by NF-{kappa}B. J. Virol. 83: 5269-5277 [Abstract] [Full Text]  
  • Johansson, P., Jansson, A., Ruetschi, U., Rymo, L. (2009). Nuclear Factor-{kappa}B Binds to the Epstein-Barr Virus LMP1 Promoter and Upregulates Its Expression. J. Virol. 83: 1393-1401 [Abstract] [Full Text]  
  • Le Clorennec, C., Ouk, T.-S., Youlyouz-Marfak, I., Panteix, S., Martin, C.-C., Rastelli, J., Adriaenssens, E., Zimber-Strobl, U., Coll, J., Feuillard, J., Jayat-Vignoles, C. (2008). Molecular Basis of Cytotoxicity of Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) in EBV Latency III B Cells: LMP1 Induces Type II Ligand-Independent Autoactivation of CD95/Fas with Caspase 8-Mediated Apoptosis. J. Virol. 82: 6721-6733 [Abstract] [Full Text]  
  • Lo, A. K. F., To, K. F., Lo, K. W., Lung, R. W. M., Hui, J. W. Y., Liao, G., Hayward, S. D. (2007). Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Natl. Acad. Sci. USA 104: 16164-16169 [Abstract] [Full Text]  


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