Research ArticleOXIDATIVE STRESS

Reactive oxygen species induce virus-independent MAVS oligomerization in systemic lupus erythematosus

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Science Signaling  29 Nov 2016:
Vol. 9, Issue 456, pp. ra115
DOI: 10.1126/scisignal.aaf1933

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Stressing out interferons

Cytosolic sensors of the RIG-I–like receptor (RLR) family bind to viral RNAs and induce oligomerization of mitochondrial antiviral signaling (MAVS) protein on the outer mitochondrial membrane. MAVS aggregation leads to the expression of genes encoding type I interferons (IFNs). Excessive type I IFN production is a hallmark of patients with systemic lupus erythematosus (SLE). Buskiewicz et al. showed that mitochondrial reactive oxygen species (ROS) induce MAVS oligomerization and type I IFN production in cells in the absence of viral infection. The MAVS-C79F variant, which is associated with decreased disease severity, failed to oligomerize in response to ROS, and cells expressing this variant exhibited reduced type I IFN production. These data suggest that oxidative stress in SLE patients may contribute to type I IFN production and could be targeted therapeutically.

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