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

Importantly, when DUSP1 silencing and JNK/p38 inhibition were combined, SeV-induced apoptosis was decreased by 23 %, showing an additive effect of the two pathways. SeV-induced apoptosis involves the intrinsic pathway leading to caspase 9 and 3 activation 62 . Therefore, to confirm the impact of JNK/p38 inhibition and/or DUSP1 silencing on SeV-induced apoptosis, . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 caspase 9 and 3 cleavage was monitored by immunoblot. Confirming the results of Annexin V, both inhibition of JNK and p38 and silencing of DUSP1 significantly impaired SeV-induced caspase 3 cleavage ( Figure 7B) . Additionally, caspase 9 cleavage that was induced following SeV infection confirming the engagement of the intrinsic pathway, was reduced in the absence of DUSP1 compared to control cells ( Figure 7B ). These findings confirmed that a JNK/p38 signaling module is involved in the induction of apoptosis during SeV infection, but they also argue against a negative regulation of this pathway by DUSP1. Rather, the observations support the hypothesis that DUSP1 is required for induction of the intrinsic apoptotic pathway independently of JNK and p38.