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Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation

Yong Shen1, Kejun Tang2, Dongdong Chen3

  • 1Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China; Department of Breast Surgery, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, P.R. China.

Cell Reports
|June 23, 2021
PubMed

Insights

Riok3, an atypical kinase, negatively regulates the type I interferon pathway, a key part of innate immunity. Its deficiency enhances antiviral responses and protects against RNA viruses by stabilizing RIG-I and MDA5.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Type I interferon (IFN) pathway is crucial for innate immunity against pathogens.
  • Precise regulation of type I IFN signaling is necessary to prevent excessive inflammation.

Purpose of the Study:

  • To investigate the role of atypical kinase Riok3 in regulating type I IFN signaling.
  • To elucidate the mechanism by which Riok3 controls antiviral innate immunity.

Main Methods:

  • Investigated Riok3's function in type I IFN signaling using in vitro assays.
  • Generated and analyzed myeloid-specific Riok3 knockout mice.
  • Examined the interaction of Riok3 with E3 ubiquitin ligase TRIM40 and its effect on RIG-I and MDA5.

Main Results:

  • Riok3 deficiency selectively inhibits RNA viral replication by upregulating type I IFN.
  • Riok3 knockout mice exhibit enhanced type I IFN induction and resistance to RNA virus infection.
  • Riok3 recruits TRIM40, leading to RIG-I and MDA5 degradation via ubiquitination.

Conclusions:

  • Riok3 acts as a negative regulator of antiviral innate immunity.
  • Riok3 targets RIG-I and MDA5 for degradation, thereby dampening the type I IFN response.
  • Understanding Riok3's mechanism provides insights into controlling viral infections.

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