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

Akira Goto*, Kiyoshi Okado, Nelson Martins, Hua Cai, Vincent Barbier, Olivier Lamiable, Laurent Troxler, Estelle Santiago, Lauriane Kuhn, Donggi Paik, Neal Silverman, Andreas Holleufer, Rune Hartmann, Jiyong Liu, Tao Peng, Jules A. Hoffmann, Carine Meignin, Laurent Daeffler, Jean-Luc Imler

*Corresponding author for this work

    Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

    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. Goto et al. show that the kinase dIKKβ and the NF-κB factor Relish control replication of picorna-like viruses in flies through induction of antiviral genes, including a homolog of STING. A STING-IKKβ-NF-κB cassette participates in resistance to picorna-like viruses, pointing to an evolutionarily ancient role of STING in antiviral immunity.

    Original languageEnglish
    JournalImmunity
    Volume49
    Issue2
    Pages (from-to)225-234.e4
    ISSN1074-7613
    DOIs
    Publication statusPublished - 21 Aug 2018

    Keywords

    • ANTIMICROBIAL PEPTIDE GENES
    • INNATE IMMUNE-RESPONSE
    • CYTOSOLIC DNA SENSOR
    • HOST-DEFENSE
    • IMD PATHWAY
    • VIRUS
    • CGAS
    • ACTIVATION
    • COMPLEX
    • PROTEIN
    • antiviral immunity
    • IKKβ
    • C19orf12
    • NF-κB
    • innate immunity
    • Dicistrovirus
    • STING
    • Drosophila melanogaster
    • IMD pathway
    • picornavirus
    • Peptide Initiation Factors/genetics
    • Drosophila Proteins/genetics
    • I-kappa B Kinase/genetics
    • Membrane Proteins/genetics
    • Dicistroviridae/immunology
    • RNA Interference
    • Transcription Factors/metabolism
    • Cell Line
    • Animals
    • Drosophila melanogaster/immunology
    • Picornaviridae Infections/immunology

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