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Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

Article scientifique 2017 Anglais

Résumé

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1, which is essential for viral genome maintenance but highly antigenic. EBV has seemingly evolved a system in which the mRNA sequence encoding the glycine-alanine repeats (GAr) of the EBNA1 protein limits its expression to the minimal level necessary for function while minimizing immune recognition. Here, we identify nucleolin (NCL) as a host factor required for this process via a direct interaction with G-quadruplexes formed in GAr-encoding mRNA sequence. Overexpression of NCL enhances GAr-based inhibition of EBNA1 protein expression, whereas its downregulation relieves the suppression of both expression and antigen presentation. Moreover, the G-quadruplex ligand PhenDC3 prevents NCL binding to EBNA1 mRNA and reverses GAr-mediated repression of EBNA1 expression and antigen presentation. Hence the NCL-EBNA1 mRNA interaction is a relevant therapeutic target to trigger an immune response against EBV-carrying cancers.

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Lista, M., Martins, R., Billant, O., Contesse, M., Findakly, S., Pochard, P., Daskalogianni, C., Beauvineau, C., Guetta, C., Jamin, C., Teulade‐Fichou, M., Fåhræus, R., Voisset, C., Blondel, M. (2017). Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA. https://doi.org/10.1038/ncomms16043

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Auteur(s)

María José Lista Rodrigo Prado Martins Olivier Billant Marie‐Astrid Contesse Sarah Findakly Pierre Pochard Chrysoula Daskalogianni Claire Beauvineau Corinne Guetta Christophe Jamin Marie‐Paule Teulade‐Fichou Robin Fåhræus Cécile Voisset Marc Blondel

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