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. Although mice deficient for MyD88, TRIF, and MAVS still moderately control NiV infection when compared with wild-type 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 represents attractive targets to develop countermeasures against severe disease induced by these pathogens.