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

Because DUSP1 preferentially dephosphorylates JNK and p38 in a variety of inflammatory contexts 39,40 , we next sought to evaluate the role of DUSP1 in the negative regulation of RSVand SeV-induced JNK and p38 activation. First, we monitored the effect of ectopically expressed DUSP1 on the SeV-and RSV-induced JNK T183/Y185 and p38 T180/Y182 phosphorylation in A549 cells. As expected, immunoblot analysis revealed that SeV ( Figure 3A and B) , and to a lesser extent RSV (Figure 3C) , induce JNK and p38 phosphorylation. Importantly, DUSP1 expression abrogates JNK and p38 phosphorylation (Figure 3A-C) . Subsequently, we confirmed the role of DUSP1 through analysis of the impact of DUSP1 silencing on the profile of virusinduced JNK and p38 phosphorylation. Immunoblot analysis confirmed the efficiency of DUSP1 silencing in A549 cells throughout the course of SeV and RSV infection (Figure 4) . Consistent with a role of DUSP1 in the dephosphorylation of JNK and p38, we observed a marked increase of JNK and p38 phosphorylation in the absence of DUSP1 during SeV ( Figure 4A ) and RSV infection ( Figure 4B) . Altogether, these observations reveal a critical role of DUSP1 in the negative regulation of JNK and p38 activation during RSV and SeV infection. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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