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

doi:10.1016/j.immuni.2018.07.013

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 › Article › peer-review

105 Citations (Scopus)

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 language	English
Pages (from-to)	225-234.e4
Journal	Immunity
Volume	49
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2018.07.013
Publication status	Published - 21 Aug 2018
Externally published	Yes

Keywords

Antiviral immunity
C19orf12
Dicistrovirus
Drosophila melanogaster
IKKβ
IMD pathway
Innate immunity
NF-κB
Picornavirus
STING

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Goto, A., Okado, K., Martins, N., Cai, H., Barbier, V., Lamiable, O., Troxler, L., Santiago, E., Kuhn, L., Paik, D., Silverman, N., Holleufer, A., Hartmann, R., Liu, J., Peng, T., Hoffmann, J. A., Meignin, C., Daeffler, L., & Imler, J. L. (2018). The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila. Immunity, 49(2), 225-234.e4. https://doi.org/10.1016/j.immuni.2018.07.013

@article{7ed2b4d7cc9a4b22ac231efce24c0908,

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

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.",

keywords = "Antiviral immunity, C19orf12, Dicistrovirus, Drosophila melanogaster, IKKβ, IMD pathway, Innate immunity, NF-κB, Picornavirus, STING",

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

note = "Funding Information: We thank Ms. A. Courtin for excellent technical assistance, P. Hamman and J. Chicher for dSTING proteomic approach, and L. Coquet and T. Jouenne for Edman degradation sequencing. Microarray analyses were performed by the IGBMC Microarray and Sequencing platform, a member of the “France G{\'e}nomique” consortium (ANR-10-INBS-0009). This work was supported by the National Institutes of Health ( PO1 AI070167 ), the Agence Nationale de la Recherche ( ANR-13-BSV3-0009 and ANR-17-CE15-0014 ), the Balzan Foundation (to J.A.H.), the Investissement d{\textquoteright}Avenir Programs ( ANR-10-LABX-0036 and ANR-11-EQPX-0022 ), the Sino-French Hoffmann Institute , CNRS , and INSERM . N.M. was supported by a Marie Sk{\l}odowska Curie fellowship. Funding Information: We thank Ms. A. Courtin for excellent technical assistance, P. Hamman and J. Chicher for dSTING proteomic approach, and L. Coquet and T. Jouenne for Edman degradation sequencing. Microarray analyses were performed by the IGBMC Microarray and Sequencing platform, a member of the “France G{\'e}nomique” consortium (ANR-10-INBS-0009). This work was supported by the National Institutes of Health (PO1 AI070167), the Agence Nationale de la Recherche (ANR-13-BSV3-0009 and ANR-17-CE15-0014), the Balzan Foundation (to J.A.H.), the Investissement d'Avenir Programs (ANR-10-LABX-0036 and ANR-11-EQPX-0022), the Sino-French Hoffmann Institute, CNRS, and INSERM. N.M. was supported by a Marie Sk{\l}odowska Curie fellowship. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = aug,

day = "21",

doi = "10.1016/j.immuni.2018.07.013",

language = "English",

volume = "49",

pages = "225--234.e4",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

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Goto, A, Okado, K, Martins, N, Cai, H, Barbier, V, Lamiable, O, Troxler, L, Santiago, E, Kuhn, L, Paik, D, Silverman, N, Holleufer, A, Hartmann, R, Liu, J, Peng, T, Hoffmann, JA, Meignin, C, Daeffler, L & Imler, JL 2018, 'The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila', Immunity, vol. 49, no. 2, pp. 225-234.e4. https://doi.org/10.1016/j.immuni.2018.07.013

TY - JOUR

T1 - The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila

AU - Goto, Akira

AU - Okado, Kiyoshi

AU - Martins, Nelson

AU - Cai, Hua

AU - Barbier, Vincent

AU - Lamiable, Olivier

AU - Troxler, Laurent

AU - Santiago, Estelle

AU - Kuhn, Lauriane

AU - Paik, Donggi

AU - Silverman, Neal

AU - Holleufer, Andreas

AU - Hartmann, Rune

AU - Liu, Jiyong

AU - Peng, Tao

AU - Hoffmann, Jules A.

AU - Meignin, Carine

AU - Daeffler, Laurent

AU - Imler, Jean Luc

N1 - Funding Information: We thank Ms. A. Courtin for excellent technical assistance, P. Hamman and J. Chicher for dSTING proteomic approach, and L. Coquet and T. Jouenne for Edman degradation sequencing. Microarray analyses were performed by the IGBMC Microarray and Sequencing platform, a member of the “France Génomique” consortium (ANR-10-INBS-0009). This work was supported by the National Institutes of Health ( PO1 AI070167 ), the Agence Nationale de la Recherche ( ANR-13-BSV3-0009 and ANR-17-CE15-0014 ), the Balzan Foundation (to J.A.H.), the Investissement d’Avenir Programs ( ANR-10-LABX-0036 and ANR-11-EQPX-0022 ), the Sino-French Hoffmann Institute , CNRS , and INSERM . N.M. was supported by a Marie Skłodowska Curie fellowship. Funding Information: We thank Ms. A. Courtin for excellent technical assistance, P. Hamman and J. Chicher for dSTING proteomic approach, and L. Coquet and T. Jouenne for Edman degradation sequencing. Microarray analyses were performed by the IGBMC Microarray and Sequencing platform, a member of the “France Génomique” consortium (ANR-10-INBS-0009). This work was supported by the National Institutes of Health (PO1 AI070167), the Agence Nationale de la Recherche (ANR-13-BSV3-0009 and ANR-17-CE15-0014), the Balzan Foundation (to J.A.H.), the Investissement d'Avenir Programs (ANR-10-LABX-0036 and ANR-11-EQPX-0022), the Sino-French Hoffmann Institute, CNRS, and INSERM. N.M. was supported by a Marie Skłodowska Curie fellowship. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2018/8/21

Y1 - 2018/8/21

N2 - 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.

AB - 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.

KW - Antiviral immunity

KW - C19orf12

KW - Dicistrovirus

KW - Drosophila melanogaster

KW - IKKβ

KW - IMD pathway

KW - Innate immunity

KW - NF-κB

KW - Picornavirus

KW - STING

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U2 - 10.1016/j.immuni.2018.07.013

DO - 10.1016/j.immuni.2018.07.013

M3 - Article

C2 - 30119996

AN - SCOPUS:85051638376

SN - 1074-7613

VL - 49

SP - 225-234.e4

JO - Immunity

JF - Immunity

IS - 2

ER -

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

Abstract

Keywords

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Correction: the kinase IKKβ Regulates a STING-and NF-κB-dependent antiviral response pathway in drosophila (immunity (2018) 49(2) (225–234.e4), (S1074761318303339), (10.1016/j.immuni.2018.07.013))

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