Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-23219-4
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Funding
- Natural Science Foundation of China [81930039, 31730026, 81525012, 81901604]
- Fundamental Research Funds of Shandong University [21510078614099]
- Fundamental Research Funds of Cheeloo College of Medicine [21510089393109]
- China Postdoctoral Science Foundation [2018M642662]
- Future Scholar Program of Shandong University
- Translational Medicine Core Facility of Shandong University
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Research demonstrates that deubiquitinase USP18 regulates MAVS-mediated antiviral signaling by promoting MAVS interaction with TRIM31, leading to increased production of type I interferon and enhanced resistance to RNA viruses.
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. Ubiquitination has an important function in the regulation of antiviral immunity involving the signalling molecule MAVS. Here the authors investigate deubiquitinating enzymes and show USP18 regulates MAVS mediated antiviral signalling through modulating the ubiquitination of MAVS via promotion of interaction between MAVS and TRIM31.
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