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

Sci Rep. 2018 Feb 27;8(1):3746. doi: 10.1038/s41598-018-22139-6.


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.

MeSH terms

  • Cell Line
  • Gene Expression
  • Gene Expression Regulation, Viral
  • Humans
  • Influenza A virus / physiology*
  • Influenza, Human / metabolism*
  • Influenza, Human / virology*
  • Protein Stability
  • Protein Transport
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism


  • INS1 protein, influenza virus
  • Tumor Suppressor Protein p53
  • Viral Nonstructural Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Ubiquitin-Protein Ligases