Abstract
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 YlY2-truncated EBNA-LP isoforms.
| Original language | English |
|---|---|
| Pages (from-to) | 7598-7607 |
| Number of pages | 10 |
| Journal | Journal of Virology |
| Volume | 81 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 15 Jul 2007 |
Bibliographical note
AcknowledgmentsWe thank Yann Lécluse for flow cytometry analysis, Abdelali Jalil for confocal microscopy, Cécile Tétaud for technical support, Pierre Busson for providing anti-LPM1 MAb and anti-IΚBα MAb, and Mounira Amor Gueret for providing anti-topoisomerase II MAb. We also thank Pierre Busson and Marc Lipinski for helpful discussions.
This work was supported by the Association pour la Recherche sur le Cancer (ARC 3454). J.G. holds a fellowship from ARC.