Epstein-Barr virus Latent Membrane Protein 1 increases calcium influx through store-operated channels in B lymphoid cells

O Dellis, A Arbabian, B Papp, Martin Rowe, I Joab, C Chomienne

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24 Citations (Scopus)


Ca2+ signaling plays an important role in B cell survival and activation and is dependent on Ca2+ trapped in the endoplasmic reticulum (ER) and on extracellular Ca2+. Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis. Previously, we showed that the ER Ca2+ 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 Ca2+ content and to increase the cytosolic Ca2+ concentration ([Ca2+](cyt)). In this follow-up study, we showed that the resting [Ca2+](cyt) of P3HR-1-infected cells was decreased, implying that EBV not only modified the ER homeostasis but also affected the cytosolic Ca2+ homeostasis. Furthermore, even if the store-operated calcium entry (SOCE) of these cells was normal, the [Ca2+](cyt) increase after thapsigargin + CaCl2 stimulation was blunted. In contrast, the resting [Ca2+](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 [Ca2+](i). Thus, EBV infection modifies the cellular Ca2+ homeostasis by acting on the ER and plasma membrane transporters.
Original languageEnglish
Pages (from-to)18583-18592
Number of pages10
JournalJournal of Biological Chemistry
Issue number21
Publication statusPublished - 27 May 2011


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