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Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane Domain Oligomerization.

Published version
Peer-reviewed

Type

Article

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Authors

Nobre, Luis 
Wise, Daniel 
Volmer, Romain 

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.

Description

Keywords

Adaptor Proteins, Signal Transducing, HEK293 Cells, Humans, Immunity, Innate, Lipid Peroxidation, Mitochondria, Protein Interaction Domains and Motifs, Reactive Oxygen Species, Recombinant Fusion Proteins, Respirovirus Infections, Sendai virus

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

PLOS
Sponsorship
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (084812/Z/08/Z)
European Commission (277713)
Wellcome Trust (093764/Z/10/Z)
This work was supported by a Wellcome Trust Intermediate Clinical Fellowship (093764 o RV), a Wellcome Trust Principal Research Fellowship (084812 to DR), a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (100140) and European Union Seventh Framework Programme Grant (Beta Bat, 277713). T