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

PloS One
Luis NobreRomain Volmer

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.

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Citations

Aug 3, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Changbo QuQiuwei Pan
May 5, 2018·Frontiers in Immunology·Alain MeyerBernard Geny
Jan 1, 2020·Scientific Reports·Alexander MoysaMichal Dadlez
Mar 7, 2021·Biomedicines·Simone PatergnaniAlessandro Rimessi
Apr 4, 2021·International Journal of Molecular Sciences·Mehdi EshraghiSaeid Ghavami

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Methods Mentioned

BETA
transfection
immunoprecipitation
Reverse Transcription PCR
Assay
Flow Cytometry

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