Wilson, J. B. , Manet, E., Gruffat, H., Busson, P., Blondel, M. and Fahraeus, R. (2018) EBNA1: oncogenic activity, immune evasion and biochemical functions provide targets for novel therapeutic strategies against Epstein-Barr virus-associated cancers. Cancers, 10(4), 109. (doi: 10.3390/cancers10040109) (PMID:29642420)
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Abstract
The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC) class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another means to cripple the virus.
Item Type: | Articles |
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Additional Information: | Research in E. Manet & H. Gruffat group is supported by the Institut National de la Santé et de la Recherche Médicale (INSERM); the Ligue Contre le Cancer, comité du Rhône; the Association pour la Recherche contre le Cancer (ARC grant no R11176CC); the LabEx Ecofect (ANR-11-LABX-0048) of the “Université de Lyon”. Research in P. Busson group is supported by the “Institut national du cancer (INCa)” (PRTk 2017 – 1RT06) and a grant "Taxe d'apprentissage Gustave Roussy - 2018 - VB". Research in M. Blondel group is supported by the following grant agencies: “La Ligue contre le cancer CSIRGO” and “Institut national du cancer (INCa)” and by Inserm and Université de Brest. Research in R. Fahraeus group is supported by Projects GACR P206/12/G151 and MEYS-NPS I-L01413, Cancerforskningsfonden Norr and Cancerfonden 160598 and “Institut national du cancer (INCa)”. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Wilson, Professor Joanna |
Authors: | Wilson, J. B., Manet, E., Gruffat, H., Busson, P., Blondel, M., and Fahraeus, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Cancers |
Publisher: | MDPI |
ISSN: | 2072-6694 |
ISSN (Online): | 2072-6694 |
Published Online: | 06 April 2018 |
Copyright Holders: | Copyright © 2018 The Authors |
First Published: | First published in Cancers 10(4):109 |
Publisher Policy: | Reproduced under a Creative Commons License |
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