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

Jinxiu Hou1, Lulu Han1, Ze Zhao2

  • 1Key Laboratory of Infection and Immunity of Shandong Province & Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, P. R. China.

Nature Communications
|May 21, 2021
PubMed

Insights

USP18 deubiquitinase enhances antiviral immunity by promoting MAVS aggregation and type I interferon production. This protein is crucial for regulating MAVS-mediated signaling against RNA viruses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • MAVS is a key adaptor in Rig-I-like receptor (RLR) signaling, essential for antiviral immunity.
  • Molecular mechanisms regulating MAVS activation, particularly ubiquitination, are not fully understood.

Purpose of the Study:

  • To investigate the role of USP18 in MAVS-mediated antiviral signaling.
  • To elucidate the molecular mechanisms by which USP18 modulates MAVS activity.

Main Methods:

  • Investigated the interaction between USP18 and MAVS.
  • Analyzed the effect of USP18 on MAVS ubiquitination and aggregation.
  • Assessed the impact of USP18 on type I interferon production and viral susceptibility in mice.

Main Results:

  • USP18 specifically interacts with MAVS and promotes its K63-linked polyubiquitination and aggregation.
  • USP18 upregulates type I interferon production in response to Sendai virus (SeV) and Encephalomyocarditis virus (EMCV) infection.
  • USP18 deficiency increases susceptibility to RNA virus infection in mice.
  • USP18 acts as a scaffold protein, facilitating TRIM31 re-localization and enhancing TRIM31-MAVS interaction.

Conclusions:

  • USP18 is a critical post-translational modulator of MAVS-mediated antiviral signaling.
  • USP18 enhances antiviral immunity by promoting MAVS activation and type I interferon production.

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