DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

Alexa C. Robitaille; Elise Caron; Nicolas Zucchini; Espérance Mukawera; Damien Adam; Mélissa K. Mariani; Anaïs Gélinas; Audray Fortin; Emmanuelle Brochiero; Nathalie Grandvaux

Next, we sought to determine whether DUSP1 belongs to the numerous negative regulators of the antiviral response induced in response to virus infections 9, 36 . First, because of their importance in the control of the IFN-mediated antiviral defense, we evaluated whether DUSP1 has an impact on the signaling cascades leading to NF-κB and IRF3 activation. Considering previous characterization of NF-κB activation in the context of RSV infection 37 , IκBα-S32 and p65-S536 phosphorylation were analyzed. Activation of IRF3 was monitored through detection of IRF3-S396 phosphorylation 38 . Ectopic expression of DUSP1 in A549 cells did not alter IκBα, p65 or IRF3 phosphorylation profiles observed during the course of SeV (Figure 2A and B) or . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 . https://doi.org/10.1101/163360 doi: bioRxiv preprint RSV infection (Figure 2C) , showing that DUSP1 does not play a role in the regulation of these defense pathways. Additionally, ectopic expression of DUSP1 in A549 cells neither significantly altered SeV N mRNA levels measured by qRT-PCR (Figure 2D top panel) nor the de novo production of RSV virions quantified by plaque assay (Figure 2D bottom panel) . Consistently, RNAi-mediated silencing of DUSP1 did not alter the capacity of RSV to replicate in A549 cells ( Figure 2E ). Together these data indicate that DUSP1 does not negatively regulate the capacity of the cell to mount an antiviral response to restrict RSV or SeV replication.