Post-translational modifications (PTMs), including phosphorylation, ubiquitylation and acetylation, of signal transduction proteins involved in the pathways engaged downstream of virus sensing are crucial to reach a fine-tuned regulation of the innate immune response 27 . In light of the very well documented importance of phosphorylation PTMs in the regulation of the antiviral response, the protein phosphatases negatively regulating the signaling events have started to be identified. The exact role of the Ser/Thr protein phosphatase 1 (PP1) in the antiviral response remains elusive as PP1α and PP1γ were found to dephosphorylate MDA-5 and RIG-I leading to their activation 28 , while they were also described to be responsible for the dephosphorylation of key C-terminal phosphoresidues of IRF3 leading to its inhibition 29 . Most . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . doi: bioRxiv preprint 15 Clement, J. F. et al. Phosphorylation of IRF-3 on Ser 339 generates a hyperactive form of IRF-3 through regulation of dimerization and CBP association.