Étude du rôle de la phosphatase DUSP1 dans la régulation de la réponse immunitaire innée autonome dans les cellules épithéliales pulmonaires lors de l'infection par le virus respiratoire syncytial et le virus Sendai
Introduction: One of the major causes of death worldwide are the lower respiratory infections, particularly those caused by viruses like the respiratory syncytial virus (RSV). To defend the host, cells produce an autonomous antiviral response that is mostly dependent on type I/III interferons to limit viral replication. They also secrete proinflammatory cytokines/chemokines to orchestrate the immune response. In order to avoid tissue damage caused by an excessive cytokine production, these responses have to be strictly regulated. Key activators of the host's defense against respiratory viruses are activated by multiple phosphorylation events, making phosphatases important negative regulators.  Results: In this Master's thesis, we study the dual-specificity phosphatase 1 (DUSP1) and its implication in the negative regulation of the host's response induced by RSV and Sendai virus (SeV). We found that DUSP1 is induced in early RSV and SeV infections in A549 cells and is subjected to proteasomal degradation. We also show that DUSP1 negatively regulates the activation of JNK and p38 MAPKs during SeV and RSV infections. Interestingly, we found that AP-1 activation and subsequent cytokine production were not modulated by DUSP1, potentially due to the protection provided by the JIP1-JNK interaction. Finally, we show for the first time that DUSP1 promotes apoptosis and suppresses cell migration.  Conclusion and relevance: Our data suggest that DUSP1 acts as a negative regulator of tissue repair mechanisms during RSV and SeV infection, making it an interesting potential therapeutic target.
DUSP1 JIP1 JNK p38 migration cytokines Pneumovirus Apoptosis Respiratory Syncytial Virus