A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness

Authors:

María José Lista1, Rodrigo Prado Martins2, Gaelle Angrand1, Alicia Quillévéré1, Chrysoula Daskalogianni2, Cécile Voisset1, Marie-Paule Teulade-Fichou3, Robin Fåhraeus2 and Marc Blondel1

doi: 10.15698/mic2017.09.590
Volume 4, pp. 305 to 307, published 31/08/2017.

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Affiliations:

1 Institut National de la Santé et de la Recherche Médicale UMR1078; Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 avenue Camille Desmoulins, F-29200 Brest, France.

2 Cibles Thérapeutiques, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, 27 rue Juliette Dodu, F-75010 Paris, France.

3 Chemistry, Modelling and Imaging for Biology, CNRS UMR9187 – Inserm U1196, Institut Curie, Université Paris-Sud, Orsay, Campus universitaire, Bat. 110, F-91405, France.

Keywords: 

Epstein-Barr virus (EBV), EBV-related cancers, EBV immune evasion, yeast model for EBV stealthiness, nucleolin (NCL).

Corresponding Author(s):

Marc Blondel, Inserm U1078; Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 avenue Camille Desmoulins, F-29200 Brest, France; Tel.: + 33 2 98018388; marc.blondel@univ-brest.fr

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

María José Lista, Rodrigo Prado Martins, Gaelle Angrand, Alicia Quillévéré, Chrysoula Daskalogianni, Cécile Voisset, Marie-Paule Teulade-Fichou, Robin Fåhraeus and Marc Blondel (2017). A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness. Microbial Cell 4(9): 305-307. doi: 10.15698/mic2017.09.590

© 2017 Lista et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome replication and maintenance but also highly antigenic. Hence, EBV evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA at a minimal level to ensure its essential function thereby, at the same time, minimizing immune recognition. Defining intervention points where to interfere with EBNA1 immune evasion is an important step to trigger an immune response against EBV-carrying cancers. Thanks to a yeast-based assay that recapitulates all the aspects of EBNA1 self-limitation of expression, a recent study by Lista et al. [Nature Communications (2017) 7, 435-444] has uncovered the role of the host cell nucleolin (NCL) in this process via a direct interaction of this protein with G-quadruplexes (G4) formed in GAr-encoding sequence of EBNA1 mRNA. In addition, the G4 ligand PhenDC3 prevents NCL binding on EBNA1 mRNA and reverses GAr-mediated repression of translation and antigen presentation. This shows that the NCL-EBNA1 mRNA interaction is a relevant therapeutic target to unveil EBV-carrying cancers to the immune system and that the yeast model can be successfully used for uncovering drugs and host factors that interfere with EBV stealthiness.