Activation of cGAS/STING pathway upon paramyxovirus infection.

Abstract

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.

• 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
• Journal: iScience (iScience) Vol. 24 Issue 6 Pg. 102519 (Jun 25 2021) ISSN: 2589-0042 [Electronic] United States
• PMID: 34142033 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors.