Abstract

The interplay between influenza A viruses (IAV) and the p53 pathway has been reported in several studies, highlighting the antiviral contribution of p53. Here, we investigated the impact of IAV on the E3-ubiquitin ligase Mdm2, a major regulator of p53, and observed that IAV targets Mdm2, notably via its non-structural protein (NS1), therefore altering Mdm2 stability, p53/Mdm2 interaction and regulatory loop during the time-course of infection. This study also highlights a new antiviral facet of Mdm2 possibly increasing the list of its many p53-independent functions. Altogether, our work contributes to better understand the mechanisms underlining the complex interactions between IAV and the p53 pathway, for which both NS1 and Mdm2 arise as key players.

Details

Title
Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection
Author
Pizzorno, Andrés 1 ; Dubois, Julia 1 ; Machado, Daniela 2 ; Cartet, Gaëlle 1 ; Traversier, Aurelien 1 ; Julien, Thomas 1 ; Bruno, Lina 3   VIAFID ORCID Logo  ; Bourdon, Jean-Christophe 4   VIAFID ORCID Logo  ; Rosa-Calatrava, Manuel 1 ; Terrier, Olivier 1   VIAFID ORCID Logo 

1  Virologie et Pathologie Humaine-VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France 
2  Virologie et Pathologie Humaine-VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; Laboratoire des Pathogènes Emergents, Fondation Mérieux. CIRI, UCBL1- INSERM U1111, ENS Lyon, Lyon, France 
3  Virologie et Pathologie Humaine-VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; Laboratoire de Virologie, Centre National de Référence des virus Influenza, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France 
4  Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom 
Pages
1-13
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-22139-6
ProQuest document ID
2010922964
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.