USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34016972.
- Also identified by DOI 10.1038/s41467-021-23219-4 and PMC identifier 8137702.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cardiovirus Infections
- Respirovirus Infections
- Ubiquitin Thiolesterase