DUSP1 promotes apoptosis and suppresses cell migration, while leaving the JIP1-protected cytokine production intact, during paramyxovirus infection.

Robitaille, A. C.; Caron, E.; Zucchini, N.; Mukawera, E.; Adam, D.; Mariani, M. K.; Gelinas, A.; Fortin, A.; Brochiero, E.; Grandvaux, N.

doi:10.1101/163360

bioRxiv · 10.1101/163360

DUSP1 promotes apoptosis and suppresses cell migration, while leaving the JIP1-protected cytokine production intact, during paramyxovirus infection.

Robitaille, A. C.·Caron, E.·Zucchini, N.·Mukawera, E.·Adam, D.·Mariani, M. K.·Gelinas, A.·Fortin, A.·Brochiero, E.·Grandvaux, N.

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Abstract

The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveil a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.

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Robitaille, A. C., Caron, E., Zucchini, N., Mukawera, E., Adam, D., Mariani, M. K., Gelinas, A., Fortin, A., Brochiero, E., Grandvaux, N.. 2017-07-13. DUSP1 promotes apoptosis and suppresses cell migration, while leaving the JIP1-protected cytokine production intact, during paramyxovirus infection.. https://doi.org/10.1101/163360

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