ZFIN ID: ZDB-PUB-200512-9
TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells
Maarifi, G., Smith, N., Maillet, S., Moncorgé, O., Chamontin, C., Edouard, J., Sohm, F., Blanchet, F.P., Herbeuval, J.P., Lutfalla, G., Levraud, J.P., Arhel, N.J., Nisole, S.
Date: 2019
Source: Science advances   5: eaax3511 (Journal)
Registered Authors: Levraud, Jean-Pierre, Lutfalla, Georges
Keywords: none
MeSH Terms:
  • Animals
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Line
  • Chikungunya virus/immunology*
  • Dendritic Cells/immunology*
  • HEK293 Cells
  • HIV-1/immunology*
  • Humans
  • Immunity, Innate/immunology
  • Influenza A Virus, H3N2 Subtype/immunology*
  • Interferon Regulatory Factor-7/metabolism
  • Interferon Type I/immunology*
  • NIMA-Interacting Peptidylprolyl Isomerase/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering/genetics
  • Signal Transduction/immunology
  • Ubiquitin-Protein Ligases/metabolism
  • Zebrafish
PubMed: 31799391 Full text @ Sci Adv
Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type I interferons (IFNs) upon viral detection. Tripartite motif (TRIM) proteins have recently come forth as important modulators of innate signaling, but their involvement in pDCs has not been investigated. Here, we performed a rationally streamlined small interfering RNA (siRNA)-based screen of TRIM proteins in human primary pDCs to identify those that are critical for the IFN response. Among candidate hits, TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function. Mechanistically, TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in an E3 ubiquitin ligase-independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1. Our findings uncover a previously unknown regulatory mechanism of type I IFN production in pDCs by which TRIM8 and Pin1 oppositely regulate the stability of pIRF7.