Activation of cGAS/STING pathway upon paramyxovirus infection

Iampietro, Mathieu; Dumont, Claire; Mathieu, Cyrille; Spanier, Julia; Robert, Jonathan; Charpenay, Aude; Dupichaud, Sébastien; Dhondt, Kévin P.; Aurine, Noémie; Pelissier, Rodolphe; Ferren, Marion; Mély, Stéphane; Gerlier, Denis; Kalinke, Ulrich; Horvat, Branka

During inflammatory diseases, cancer and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV) and Measles virus (MeV), can also trigger the cGAS/STING axis. While mice deficient for MyD88, TRIF and MAVS still moderately control NiV infection when compared to WT mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type-I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection, and possibly represent attractive targets to develop countermeasures against severe disease induced by these pathogens.