The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila

Immunity. 2018 Aug 21;49(2):225-234.e4. doi: 10.1016/j.immuni.2018.07.013. Epub 2018 Aug 14.

Abstract

Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity.

Keywords: C19orf12; Dicistrovirus; Drosophila melanogaster; IKKβ; IMD pathway; NF-κB; STING; antiviral immunity; innate immunity; picornavirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dicistroviridae / immunology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / virology*
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • Picornaviridae Infections / immunology*
  • RNA Interference
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • Nazo protein, Drosophila
  • Peptide Initiation Factors
  • Rel protein, Drosophila
  • Transcription Factors
  • aub protein, Drosophila
  • I-kappa B Kinase

Supplementary concepts

  • Drosophila C virus