Modulation of b-cell endoplasmic reticulum calcium homeostasis by epstein-barr virus latent membrane protein-1

Olivier Dellis, Atousa Arbabian, Jean Philippe Brouland, T. Kovács, Martin Rowe, Christine Chomienne, Irène Joab, Béla Papp

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number1476
Pages (from-to)59
Number of pages1
JournalMolecular Cancer
Volume8
DOIs
Publication statusPublished - Aug 3 2009

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Endoplasmic Reticulum
Homeostasis
B-Lymphocytes
Calcium
Human Herpesvirus 4
Viruses
Enzymes
CD80 Antigens
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Epstein-Barr virus EBV-associated membrane antigen
Germinal Center
Calcium Signaling
Burkitt Lymphoma
Viral Genes
Calcium-Transporting ATPases
Inositol
Lymphocyte Activation
Infection
Transgenes
Protein Isoforms

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Modulation of b-cell endoplasmic reticulum calcium homeostasis by epstein-barr virus latent membrane protein-1. / Dellis, Olivier; Arbabian, Atousa; Brouland, Jean Philippe; Kovács, T.; Rowe, Martin; Chomienne, Christine; Joab, Irène; Papp, Béla.

In: Molecular Cancer, Vol. 8, 1476, 03.08.2009, p. 59.

Research output: Contribution to journalArticle

Dellis, Olivier ; Arbabian, Atousa ; Brouland, Jean Philippe ; Kovács, T. ; Rowe, Martin ; Chomienne, Christine ; Joab, Irène ; Papp, Béla. / Modulation of b-cell endoplasmic reticulum calcium homeostasis by epstein-barr virus latent membrane protein-1. In: Molecular Cancer. 2009 ; Vol. 8. pp. 59.
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AU - Rowe, Martin

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