Journal article
Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells
L Fitzsimmons, AJ Boyce, W Wei, C Chang, D Croom-Carter, RJ Tierney, MJ Herold, AI Bell, A Strasser, GL Kelly, M Rowe
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2018
DOI: 10.1038/cdd.2017.150
Abstract
While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clo..
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Grants
Awarded by Cancer Research UK
Funding Acknowledgements
We thank Profs Kenzo Takada and Teru Kanda for provision of the Akata-BL cell line, the pEKS10 plasmid and recombinant Akata-GFP2-producing Akata-BL cells; Tracey Haigh and Dr. Graham Taylor for cloning EBNA1 into the FTrex-UTG lentivirus; Dr. Toru Okamoto for generating the BIMS variant expressing lentiviruses and Giovanni Sicilano, Carmen Gatt and Hannah Johnson for mouse husbandry. We are also grateful to Prof. Alan Rickinson for critical reading of the manuscript. This work was supported by funding from: the Kay Kendall Leukaemia Fund Fellowship KKL331 awarded to GLK; Cancer Research UK, Programme Grant C5575/A15032 awarded to MR; Cancer Council Victoria, grant-in-aid no. 1086157 awarded to GLK; the National Health and Medical Research Council, Project Grant No. 1086291 awarded to GLK, Program Grant No. 101671 awarded to AS, Fellowship No. 1020363 awarded to AS; the Leukaemia and Lymphoma Society, Grant No. 7001-13 awarded to AS; and the estate of Anthony (Toni) Redstone OAM.