Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

Andrés Pizzorno; Julia Dubois; Daniela Machado; Gaëlle Cartet; Aurelien Traversier; Thomas Julien; Bruno Lina; Jean-Christophe Bourdon; Manuel Rosa-Calatrava; Olivier Terrier

doi:10.1038/s41598-018-22139-6

Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

Andrés Pizzorno, Julia Dubois, Daniela Machado, Gaëlle Cartet, Aurelien Traversier, Thomas Julien, Bruno Lina, Jean-Christophe Bourdon, Manuel Rosa-Calatrava, Olivier Terrier (Lead / Corresponding author)

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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.

Original language	English
Article number	3746
Pages (from-to)	1-13
Number of pages	13
Journal	Scientific Reports
Volume	8
DOIs	https://doi.org/10.1038/s41598-018-22139-6
Publication status	Published - 27 Feb 2018

Keywords

Journal article
Influenza virus
Virus-host interactions

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10.1038/s41598-018-22139-6Licence: CC BY

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Cite this

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title = "Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection",

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.",

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AU - Pizzorno, Andrés

AU - Dubois, Julia

AU - Machado, Daniela

AU - Cartet, Gaëlle

AU - Traversier, Aurelien

AU - Julien, Thomas

AU - Lina, Bruno

AU - Bourdon, Jean-Christophe

AU - Rosa-Calatrava, Manuel

AU - Terrier, Olivier

N1 - No funding info

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Y1 - 2018/2/27

N2 - 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.

AB - 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.

KW - Journal article

KW - Influenza virus

KW - Virus-host interactions

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JF - Scientific Reports

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Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

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Bourdon, Jean-Christophe

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Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection

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Bourdon, Jean-Christophe

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