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

Détails

ID Serval
serval:BIB_AADC2AE853AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus latent membrane protein-1.
Périodique
Molecular Cancer
Auteur(s)
Dellis O., Arbabian A., Brouland J.P., Kovàcs T., Rowe M., Chomienne C., Joab I., Papp B.
ISSN
1476-4598 (Electronic)
ISSN-L
1476-4598
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
8
Pages
59
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Résumé
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.
Mots-clé
B-Lymphocytes/cytology, B-Lymphocytes/metabolism, Blotting, Western, Burkitt Lymphoma/metabolism, Burkitt Lymphoma/pathology, Calcium/metabolism, Cell Line, Tumor, Cell Transformation, Viral, Endoplasmic Reticulum/metabolism, Epstein-Barr Virus Nuclear Antigens/genetics, Epstein-Barr Virus Nuclear Antigens/metabolism, Herpesvirus 4, Human/genetics, Herpesvirus 4, Human/metabolism, Homeostasis, Humans, Immunohistochemistry, Lymphocyte Activation, Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism, Viral Matrix Proteins/genetics, Viral Matrix Proteins/metabolism, Viral Proteins/genetics, Viral Proteins/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/10/2015 9:57
Dernière modification de la notice
20/08/2019 15:14
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