Chicken DNA virus sensor DDX41 activates IFN-β signaling pathway dependent on STING

Dev Comp Immunol. 2017 Nov:76:334-342. doi: 10.1016/j.dci.2017.07.001. Epub 2017 Jul 3.

Abstract

The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here, we report the identification of the first avian DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), an important DNA sensor, in chicken cells. In our study, we confirmed that chDDX41 is not an interferon-inducible gene. Knockdown of chDDX41 expression by shRNA blocked the ability of DF-1 cells to mount an IFN-β response to DNA and associated viruses. ChDDX41 mRNAs could be upregulated by double-stranded DNA (dsDNA) analogue poly(dA:dT), but not by double-stranded RNA (dsRNA) analogue poly(I:C). In poly(dA:dT) stimulation assays, the immune molecules involved in the DDX41-mediated IFN-β pathway in human cells were universally upregulated in chicken cells. Via coimmunoprecipitation (Co-IP) experiments, we found that chDDX41 could strongly interact with chicken stimulator of IFN genes (chSTING). Therefore, our results suggest that chDDX41 is involved in the dsDNA- and dsDNA virus-mediated chDDX41-chSTING-IFN-β signaling pathway in chicken cells.

Keywords: Chicken; DDX41; DNA sensor; DNA virus; IFN-β; STING.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism*
  • Cell Line
  • Chickens
  • Cloning, Molecular
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • DNA Viruses / immunology*
  • Fibroblasts / metabolism*
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Interferon-gamma / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Virus Diseases / immunology*

Substances

  • Avian Proteins
  • Interferon Regulatory Factors
  • RNA, Small Interfering
  • Interferon-gamma
  • DDX41 protein, human
  • DEAD-box RNA Helicases