Factor inhibiting HIF negatively regulates antiviral innate immunity via hydroxylation of IKKϵ.

CP: Immunology FIH IKKϵ MAVS TBK1 TRAF3 hydroxylation hypoxia innate immunity mouse zebrafish

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 Dec 2023
Historique:
received: 23 01 2023
revised: 20 10 2023
accepted: 06 12 2023
medline: 21 12 2023
pubmed: 21 12 2023
entrez: 21 12 2023
Statut: aheadofprint

Résumé

Activation of type I interferon (IFN-1) signaling is essential to protect host cells from viral infection. The full spectrum of IFN-I induction requires the activation of a number of cellular factors, including IκB kinase epsilon (IKKϵ). However, the regulation of IKKϵ activation in response to viral infection remains largely unknown. Here, we show that factor inhibiting hypoxia-inducible factor (HIF) (FIH), an asparaginyl hydroxylase, interacts with IKKϵ and catalyzes asparagine hydroxylation of IKKϵ at Asn-254, Asn-700, and Asn-701, resulting in the suppression of IKKϵ activation. FIH-mediated hydroxylation of IKKϵ prevents IKKϵ binding to TBK1 and TRAF3 and attenuates the cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex-catalyzed K63-linked polyubiquitination of IKKϵ at Lys-416. In addition, Fih-deficient mice and zebrafish are more resistant to viral infection. This work uncovers a previously unrecognized role of FIH in suppressing IKKϵ activation for IFN signaling and antiviral immune responses.

Identifiants

DOI: 10.1016/j.celrep.2023.113606 PMID: 38127621
pubmed: 38127621
pii: S2211-1247(23)01618-2
doi: 10.1016/j.celrep.2023.113606
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113606

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Xiaolian Cai (X)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China.

Rui Wang (R)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; College of Fisheries and Life Science, Dalian Ocean University, Dalian 116000, P.R. China.

Junji Zhu (J)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China.

Xiong Li (X)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Xing Liu (X)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Gang Ouyang (G)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China.

Jing Wang (J)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Zhi Li (Z)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.

Chunchun Zhu (C)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China.

Hongyan Deng (H)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China.

Wuhan Xiao (W)

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P.R. China; Hubei Hongshan Laboratory, Wuhan 430070, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China. Electronic address: w-xiao@ihb.ac.cn.

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