USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS.

Activation of MAVS, an adaptor molecule in Rig-I-like receptor (RLR) signaling, is indispensable for antiviral immunity, yet the molecular mechanisms modulating MAVS activation are not completely understood. Ubiquitination has a central function in regulating the activity of MAVS. Here, we demonstrate that a mitochondria-localized deubiquitinase USP18 specifically interacts with MAVS, ...
promotes K63-linked polyubiquitination and subsequent aggregation of MAVS. USP18 upregulates the expression and production of type I interferon following infection with Sendai virus (SeV) or Encephalomyocarditis virus (EMCV). Mice with a deficiency of USP18 are more susceptible to RNA virus infection. USP18 functions as a scaffold protein to facilitate the re-localization of TRIM31 and enhances the interaction between TRIM31 and MAVS in mitochondria. Our results indicate that USP18 functions as a post-translational modulator of MAVS-mediated antiviral signaling.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cardiovirus Infections, Cell Line, Tumor, Disease Models, Animal, Encephalomyocarditis virus, Gene Knockdown Techniques, HEK293 Cells, Humans, Immunity, Innate, Interferon Type I, Lysine, Male, Mice, Mice, Knockout, Protein Processing, Post-Translational, RAW 264.7 Cells, Recombinant Proteins, Respirovirus Infections, Sendai virus, Signal Transduction, Tripartite Motif Proteins, Ubiquitin Thiolesterase, Ubiquitin-Protein Ligases, Ubiquitination
Nat Commun
Date: Dec. 20, 2020
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