title: Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane Domain Oligomerization.
abstract: RIG-I-like receptors detect viral RNA in infected cells and promote oligomerization of the outer mitochondrial membrane protein MAVS to induce innate immunity to viral infection through type I interferon production. Mitochondrial reactive oxygen species (mROS) have been shown to enhance anti-viral MAVS signalling, but the mechanisms have remained obscure. Using a biochemical oligomerization-reporter fused to the transmembrane domain of MAVS, we found that mROS inducers promoted lipid-dependent MAVS transmembrane domain oligomerization in the plane of the outer mitochondrial membrane. These events were mirrored by Sendai virus infection, which similarly induced lipid peroxidation and promoted lipid-dependent MAVS transmembrane domain oligomerization. Our observations point to a role for mROS-induced changes in lipid bilayer properties in modulating antiviral innate signalling by favouring the oligomerization of MAVS transmembrane domain in the outer-mitochondrial membrane.
authors: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust MRC Institute of Metabolic Science, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
authors: Luis
authors: L
authors: Nobre
authors: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust MRC Institute of Metabolic Science, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
authors: Daniel
authors: D
authors: Wise
authors: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust MRC Institute of Metabolic Science, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
authors: David
authors: D
authors: Ron
authors: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust MRC Institute of Metabolic Science, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom; Université de Toulouse, INP, ENVT, UMR1225, IHAP, F-31076 Toulouse, France; INRA, UMR1225, IHAP, F-31076 Toulouse, France.
authors: Romain
authors: R
authors: Volmer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D010253:Respirovirus Infections / Q000276:immunology; D029082:Sendai virus / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins