RNF19a inhibits antiviral immune response to RNA viruses through degradation of TBK1

Mol Immunol. 2022 Mar:143:1-6. doi: 10.1016/j.molimm.2021.12.021. Epub 2022 Jan 3.

Abstract

TANK-binding kinase 1 (TBK1) plays a pivotal role in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/β) and of NF-κB signal transduction following viral infections. TBK1 must be tightly regulated to effectively control viral infections and maintain immune homeostasis. Here, we found that E3 ubiquitin ligase RNF19a mediated K48-linked ubiquitination and proteasomal degradation of TBK1. Specifically, the silence of RNF19a enhanced the production of type I interferons and suppressed RNA viral replication. Our results uncover that RNF19a acts as a negative mediator in the RIG-I signaling pathway to attenuate antiviral immune responses and suggest RNF19a as a potential therapy target in clinical infectious and inflammatory diseases.

Keywords: Innate immune; Proteasomal degradation; RNF19a; TBK1; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / immunology*
  • Herpesvirus 1, Human / physiology
  • Immunity*
  • Interferon Type I / metabolism
  • Lysine / metabolism
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteolysis*
  • RNA Viruses / immunology*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Vesiculovirus / physiology

Substances

  • Antiviral Agents
  • Interferon Type I
  • Rnf19a protein, mouse
  • Ubiquitin-Protein Ligases
  • Tbk1 protein, mouse
  • Protein Serine-Threonine Kinases
  • Lysine