Switch in post-translational modifications upon Influenza virus infection

Abstract

Influenza is an acute respiratory disease caused by influenza virus that affects millions of individuals and causes the death of more than 300,000 people every year. It is well known that the severity of the disease depends on both virus and host factors. The host response to influenza virus infection is necessary for viral clearance but influenza virus manipulates the machinery of the infected cells to improve virus replication. The outcome of this battle determines the evolution and severity of the disease. Here we have studied influenza virus-host cell interactions in order to decipher the molecular mechanisms of the disease. We have focussed on the role that post-translational modifications play in these interactions. Our data revealed that activation of eIF5A plays is key for influenza A virus replication (as well as in replication of other viruses). We identified both SUMOylation and NEDDylation as novel mechanisms to control eIF5A activity, and demonstrated the critical role of eIF5A SUMOylation on the cellular response to different types of stress. Furthermore, we identified the influenza virus NS1 protein as well as several cellular proteins as targets for NEDD8 conjugation upon influenza virus infection, and deciphered the role of NS1 NEDDylation in the antiviral activity mediated by the viral protein. Finally, we demonstrated, for the first time, an interplay between UFMylation and influenza virus replication. Our data revealed that UFM1 is a key factor for influenza virus replication. In summary, this work demonstrates the importance of post-translational modifications in influenza virus-host cell interplay.