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

Ectopically expressed JIP1 coimmunoprecipitated with endogenous JNK, both in uninfected and SeV-and RSV-infected cells ( Figure 5A ). By contrast, JIP3 did not interact with JNK ( Figure 5A ). Since we demonstrated the existence of a JIP1/JNK complex, we examined the role of JIP1 in the regulation of DUSP1 dephosphorylation during SeV and RSV infection. A549 cells were cotransfected with JIP1 together with empty or DUSP1-expressing constructs before infection with SeV ( Figure 5B ) or RSV ( Figure 5C ). Confirming our finding (Figure 3) , ectopic expression of DUSP1 resulted in inhibition of SeV-and RSV-induced JNK phosphorylation (Figure 5B and C). Importantly, when JIP1 was coexpressed with DUSP1, the levels of phosphorylated JNK was increased 5.9 and 4 times compared to cells transfected with DUSP1 only during SeV and RSV infection, respectively ( Figure 5D ). Collectively, these data demonstrate that JIP1 interacts with JNK and that recruitment of JNK by JIP1 prevents dephosphorylation by DUSP1 during SeV and RSV 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 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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