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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.
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Luis Nobre, Daniel Wise, David Ron, Romain Volmer. Modulation of innate immune signalling by lipid-mediated MAVS transmembrane domain oligomerization. PLoS ONE, Public Library of Science, 2015, 10 (8), ⟨10.1371/journal.pone.0136883⟩. ⟨hal-02632377⟩

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