Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus latent membrane protein-1.

Abstract : BACKGROUND: Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-tris-phosphate-induced release of calcium stored in the endoplasmic reticulum (ER). Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes), and therefore these enzymes play an important role in ER calcium homeostasis and in the control of B of cell activation. Because Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis, in this work the effects of the virus on SERCA-type calcium pump expression and calcium accumulation in the endoplasmic reticulum of B cells was investigated. RESULTS: Two Sarco-Endoplasmic Reticulum Calcium transport ATPase isoforms, the low Ca2+-affinity SERCA3, and the high Ca2+-affinity SERCA2 enzymes are simultaneously expressed in B cells. Latency type III infection of Burkitt's lymphoma cell lines with immortalization-competent virus expressing the full set of latency genes selectively decreased the expression of SERCA3 protein, whereas infection with immortalization-deficient virus that does not express the EBNA2 or LMP-1 viral genes was without effect. Down-modulation of SERCA3 expression could be observed upon LMP-1, but not EBNA2 expression in cells carrying inducible transgenes, and LMP-1 expression was associated with enhanced resting cytosolic calcium levels and increased calcium storage in the endoplasmic reticulum. Similarly to virus-induced B cell immortalisation, SERCA3 expression was also decreased in normal B cells undergoing activation and blastic transformation in germinal centers of lymph node follicles. CONCLUSION: The data presented in this work indicate that EBV-induced immortalization leads to the remodelling of ER calcium homeostasis of B cells by LMP-1 that copies a previously unknown normal phenomenon taking place during antigen driven B cell activation. The functional remodelling of ER calcium homeostasis by down-regulation of SERCA3 expression constitutes a previously unknown mechanism involved in EBV-induced B cell immortalisation.
Type de document :
Article dans une revue
Molecular Cancer, BioMed Central, 2009, 8 (1), pp.59. 〈10.1186/1476-4598-8-59〉
Liste complète des métadonnées

Littérature citée [65 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00663619
Contributeur : Ed. Bmc <>
Soumis le : vendredi 27 janvier 2012 - 13:47:54
Dernière modification le : jeudi 9 février 2017 - 15:52:25
Document(s) archivé(s) le : mercredi 14 décembre 2016 - 02:32:20

Fichiers

1476-4598-8-59.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Olivier Dellis, Atousa Arbabian, Jean-Philippe Brouland, Tünde Kovàcs, Martin Rowe, et al.. Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus latent membrane protein-1.. Molecular Cancer, BioMed Central, 2009, 8 (1), pp.59. 〈10.1186/1476-4598-8-59〉. 〈inserm-00663619〉

Partager

Métriques

Consultations de la notice

289

Téléchargements de fichiers

181