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

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Listed:
  • María José Lista

    (Institut National de la Santé et de la Recherche Médicale UMR1078; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire
    Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé)

  • Rodrigo Prado Martins

    (Cibles Thérapeutiques, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire)

  • Olivier Billant

    (Institut National de la Santé et de la Recherche Médicale UMR1078; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire
    Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé)

  • Marie-Astrid Contesse

    (Institut National de la Santé et de la Recherche Médicale UMR1078; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire
    Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé)

  • Sarah Findakly

    (Cibles Thérapeutiques, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire)

  • Pierre Pochard

    (Inserm UMR 1227, Lymphocytes B et Autoimmunité; CHRU Brest, Hôpital Morvan, Laboratoire d’Immunologie
    Université de Bretagne Occidentale)

  • Chrysoula Daskalogianni

    (Cibles Thérapeutiques, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire)

  • Claire Beauvineau

    (Chemistry, Modelling and Imaging for Biology, CNRS UMR9187 - Inserm U1196, Institut Curie, Université Paris-Sud)

  • Corinne Guetta

    (Chemistry, Modelling and Imaging for Biology, CNRS UMR9187 - Inserm U1196, Institut Curie, Université Paris-Sud)

  • Christophe Jamin

    (Inserm UMR 1227, Lymphocytes B et Autoimmunité; CHRU Brest, Hôpital Morvan, Laboratoire d’Immunologie
    Université de Bretagne Occidentale)

  • Marie-Paule Teulade-Fichou

    (Chemistry, Modelling and Imaging for Biology, CNRS UMR9187 - Inserm U1196, Institut Curie, Université Paris-Sud)

  • Robin Fåhraeus

    (Cibles Thérapeutiques, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire)

  • Cécile Voisset

    (Institut National de la Santé et de la Recherche Médicale UMR1078; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire
    Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé)

  • Marc Blondel

    (Institut National de la Santé et de la Recherche Médicale UMR1078; Etablissement Français du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire
    Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé)

Abstract

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.

Suggested Citation

  • María José Lista & Rodrigo Prado Martins & Olivier Billant & Marie-Astrid Contesse & Sarah Findakly & Pierre Pochard & Chrysoula Daskalogianni & Claire Beauvineau & Corinne Guetta & Christophe Jamin &, 2017. "Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16043
    DOI: 10.1038/ncomms16043
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