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

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

Author information

1
Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), 67084 Strasbourg, France; Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: goto@unistra.fr.
2
Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), 67084 Strasbourg, France.
3
Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), 67084 Strasbourg, France; Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China.
4
Université de Strasbourg, CNRS, Plateforme Protéomique Strasbourg-Esplanade, 67000 Strasbourg, France.
5
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
6
Center for Structural Biology, Aarhus University, 8000 Aarhus C, Denmark.
7
Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China.
8
Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), 67084 Strasbourg, France; Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China; University of Strasbourg Institute for Advanced Study, 67000 Strasbourg, France.
9
Université de Strasbourg, CNRS, Insect Models of Innate Immunity (M3I; UPR9022), 67084 Strasbourg, France; Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: jl.imler@unistra.fr.

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

PMID:
30119996
PMCID:
PMC6267954
DOI:
10.1016/j.immuni.2018.07.013
[Indexed for MEDLINE]
Free PMC Article

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