Activation of cGAS/STING pathway upon paramyxovirus infection

• Main Authors: Mathieu Iampietro, Claire Dumont, Cyrille Mathieu, Julia Spanier, Jonathan Robert, Aude Charpenay, Sébastien Dupichaud, Kévin P. Dhondt, Noémie Aurine, Rodolphe Pelissier, Marion Ferren, Stéphane Mély, Denis Gerlier, Ulrich Kalinke, Branka Horvat
• Format: Article
• Language: English
• Published: Elsevier 2021-06-01
• Series: iScience
• Subjects: immune system; molecular biology; Virology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221004879

Summary: 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.