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

Scientific Reports
Andrés PizzornoOlivier Terrier

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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Citations

Aug 29, 2018·Journal of Medical Virology·Hany KhalilSamir El-Masry
Apr 20, 2018·Human Vaccines & Immunotherapeutics·Alberto Pérez Rubio, Jose María Eiros
Jul 28, 2020·Critical Reviews in Microbiology·Chengye LiFanhua Wei
Oct 6, 2020·The Journal of General Virology·Yucen LiXin Ye
Apr 24, 2021·Genes & Development·Alyssa M KleinCarol Prives

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Methods Mentioned

BETA
ubiquitination
confocal microscopy
co-immunoprecipitation assay
transfection
scraping
Assay
transfections

Software Mentioned

Graphpad Prism
ImageJ

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