title: Epstein-Barr virus latent membrane protein 1 increases calcium influx through store-operated channels in B lymphoid cells.
abstract: Ca(2+) signaling plays an important role in B cell survival and activation and is dependent on Ca(2+) trapped in the endoplasmic reticulum (ER) and on extracellular Ca(2+). Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis. Previously, we showed that the ER Ca(2+) content of Burkitt lymphoma cell lines was increased following infection with immortalization-competent virus expressing the full set of EBV latency genes (B95-8). In contrast, infection with an immortalization-deficient virus (P3HR-1) not expressing LMP-1 is without effect. LMP-1 protein expression was sufficient to increase the ER Ca(2+) content and to increase the cytosolic Ca(2+) concentration ([Ca(2+)](cyt)). In this follow-up study, we showed that the resting [Ca(2+)](cyt) of P3HR-1-infected cells was decreased, implying that EBV not only modified the ER homeostasis but also affected the cytosolic Ca(2+) homeostasis. Furthermore, even if the store-operated calcium entry (SOCE) of these cells was normal, the [Ca(2+)](cyt) increase after thapsigargin + CaCl(2) stimulation was blunted. In contrast, the resting [Ca(2+)](cyt) of B95-8 infected cells was not changed, even if their SOCE was increased significantly. When expressed alone, LMP-1 induced an increase of the SOCE amplitude and the expression of the protein allowing this influx, Orai1, showing the effect of EBV on SOCE of B cells are mediated by LMP-1. However, other hitherto unidentified EBV processes, unmasked in P3HR-1 infected cells, counteract this LMP-1-dependent increase of SOCE amplitude to impair a general and potentially toxic increase of [Ca(2+)](i). Thus, EBV infection modifies the cellular Ca(2+) homeostasis by acting on the ER and plasma membrane transporters.
authors: Institut National de la Santé et de la Recherche Médicale, INSERM UMR-S 940, Institut Universitaire d'Hématologie, Université Paris VII, Paris, France. olivier.dellis@inserm.fr
authors: Olivier
authors: O
authors: Dellis
authors: Atousa
authors: A
authors: Arbabian
authors: Béla
authors: B
authors: Papp
authors: Martin
authors: M
authors: Rowe
authors: Irène
authors: I
authors: Joab
authors: Christine
authors: C
authors: Chomienne
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071740:ORAI1 Protein; D019284:Thapsigargin / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D004791:Enzyme Inhibitors; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D014763:Viral Matrix Proteins; D019284:Thapsigargin; D002118:Calcium