USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS.
Nat Commun
; 12(1): 2970, 2021 05 20.
Article
em En
| MEDLINE
| ID: mdl-34016972
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.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Respirovirus
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Infecções por Cardiovirus
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Ubiquitina Tiolesterase
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Proteínas Adaptadoras de Transdução de Sinal
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article