Chicken TBK1 interacts with STING and is involved in IFN-β signaling regulation

Dev Comp Immunol. 2017 Dec:77:200-209. doi: 10.1016/j.dci.2017.08.011. Epub 2017 Aug 22.

Abstract

TANK-binding kinase 1 (TBK1) is an essential serine/threonine-protein kinase required for the Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I) -mediated induction of type I IFN. Through endogenous Co-IP and LC-MS/MS, we identified chicken TBK1 (chTBK1) as a chSTING-interactive protein. Through exogenous Co-IP assay in transfected cells, we confirmed the interaction between chSTING and chTBK1. To better understand the biological role of chTBK1 in the chSTING-mediated IFN pathway, we cloned the chTBK1 and investigated its biological functions. Quantitative RT-PCR showed that chTBK1 mRNA was widely expressed in different tissues. The overexpression of chTBK1 in DF-1 cells induced the expression of IFN-β and ISGs and inhibited AIV viral replication. We identified indispensable domains of chTBK1 on IFN-β production via the generation of various chTBK1 mutant forms. Together, we identified the chTBK1 as a chSTING interactive protein and concluded that chTBK1 is involved in chSTING-triggered IFN-β signaling in chicken cells.

Keywords: Avian influenza viruses; Chicken; IFN-β; Stimulator of interferon genes; TANK-Binding kinase 1.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism*
  • Cell Line
  • Chickens / genetics
  • Chickens / immunology*
  • Humans
  • Immunity, Innate
  • Influenza A virus / physiology*
  • Influenza in Birds / immunology*
  • Interferon-beta / metabolism*
  • Membrane Proteins / genetics
  • Mutation
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Transgenes / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Avian Proteins
  • Membrane Proteins
  • STING1 protein, human
  • Interferon-beta
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human