Multifaceted activation of STING axis upon Nipah and measles virus-induced syncytia formation
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.
Authors
- Rodolphe Pélissier (ORCID: https://orcid.org/0000-0002-9878-029X)
- Dániel Déri (ORCID: https://orcid.org/0000-0002-9078-4923)
- Ulrich Kalinke (ORCID: https://orcid.org/0000-0003-0503-9564)
- Jennifer Skerra (ORCID: https://orcid.org/0000-0002-8845-7683)
- Olivier Reynard (ORCID: https://orcid.org/0000-0001-7536-355X)
- Mathieu Iampietro (ORCID: https://orcid.org/0000-0002-8946-3049)
- Claudia González (ORCID: https://orcid.org/0000-0002-0855-939X)
- L. Karkowski
- Cyrille Mathieu (ORCID: https://orcid.org/0000-0002-6682-2029)
- Claire Dumont (ORCID: https://orcid.org/0000-0001-7511-1512)
- Julia Spanier (ORCID: https://orcid.org/0000-0002-8797-3563)
- Branka Horvat (ORCID: https://orcid.org/0000-0003-0578-7765)
- Zoltán Kis (ORCID: https://orcid.org/0000-0002-6598-8369)
- Lucia Amurri (ORCID: https://orcid.org/0000-0002-3257-3140)
- Bernadett Pályi (ORCID: https://orcid.org/0000-0003-1975-4198)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Semmelweis University (HU)
- École Normale Supérieure de Lyon (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- European Research Council (BE)
- National Public Health and Medical Officer Service (HU)
- Center for Experimental and Clinical Infection Research (DE)
- Centre International de Recherche en Infectiologie (FR)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1371/journal.ppat.1012569
- Citations
- 7
- Primary Topic
- Virology and Viral Diseases
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Alliance Nationale pour les Sciences de la Vie et de la Santé
- European Commission
- Institut National de la Santé et de la Recherche Médicale
- Semmelweis Egyetem
- Universiti Malaya
- Centre National de la Recherche Scientifique
- École Normale Supérieure de Lyon
- Direction Générale de l’Armement