Frontiers in Immunology (Sep 2020)

The Ubiquitin E3 Ligase Parkin Inhibits Innate Antiviral Immunity Through K48-Linked Polyubiquitination of RIG-I and MDA5

  • Lang Bu,
  • Huan Wang,
  • Panpan Hou,
  • Shuting Guo,
  • Miao He,
  • Jingshu Xiao,
  • Ping Li,
  • Yongheng Zhong,
  • Penghui Jia,
  • Yuanyuan Cao,
  • Guanzhan Liang,
  • Chenwei Yang,
  • Lang Chen,
  • Deyin Guo,
  • Chun-Mei Li

DOI
https://doi.org/10.3389/fimmu.2020.01926
Journal volume & issue
Vol. 11

Abstract

Read online

Innate immunity is the first-line defense against antiviral or antimicrobial infection. RIG-I and MDA5, which mediate the recognition of pathogen-derived nucleic acids, are essential for production of type I interferons (IFN). Here, we identified mitochondrion depolarization inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibited the response and antiviral activity of type I IFN during viral infection. Furthermore, we found that the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin mediated mitophagy, thus negatively regulating the activation of RIG-I and MDA5. Parkin directly interacted with and catalyzed the K48-linked polyubiquitination and subsequent degradation of RIG-I and MDA5. Thus, we demonstrate that Parkin limits RLR-triggered innate immunity activation, suggesting Parkin as a potential therapeutic target for the control of viral infection.

Keywords