Activation of cGAS/STING pathway upon paramyxovirus infection

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

doi:10.1016/j.isci.2021.102519

Activation of cGAS/STING pathway upon paramyxovirus infection

iScience. 2021 May 7;24(6):102519. doi: 10.1016/j.isci.2021.102519. eCollection 2021 Jun 25.

Authors

Affiliations

¹ CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon, 21 Avenue Tony Garnier, 69007 Lyon, France.
² Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection research, a joint venture between the Hanover Medical School and the Helmholtz Centre for Infection Research, Hanover, Germany.
³ INSERM- Laboratoire P4 Jean Mérieux-21 Avenue Tony Garnier, 69365 Lyon, France.
⁴ Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hanover, Germany.

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.

Keywords: Virology; immune system; molecular biology.