Multifaceted activation of STING axis upon Nipah and measles virus-induced syncytia formation

by Lucia Amurri, Claire Dumont, Rodolphe Pelissier, Olivier Reynard, Cyrille Mathieu, Julia Spanier, Bernadett Pályi, Daniel Déri, Ludovic Karkowski, Claudia Gonzalez, Jennifer Skerra, Zoltán Kis, Ulrich Kalinke, Branka Horvat, Mathieu Iampietro

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNβ and interleukin 6. Finally, we found that paramyxovirus-induced syncytia formation is responsible for loss of mitochondrial membrane potential and leakage of mitochondrial DNA in the cytoplasm, the latter of which is further detected by both cGAS and IFI16. These results contribute to improve our understanding about NiV and MeV immunopathogenesis and provide potential paths for alternative therapeutic strategies.