Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3

Xing Liu, Jinhua Tang, Zixuan Wang, Chunchun Zhu, Hongyan Deng, Xueyi Sun, Guangqing Yu, Fangjing Rong, Xiaoyun Chen, Qian Liao, Shuke Jia, Wen Liu, Huangyuan Zha, Sijia Fan, Xiaolian Cai, Jian-Fang Gui and Wuhan Xiao ()
Additional contact information
Xing Liu: Chinese Academy of Sciences
Jinhua Tang: Chinese Academy of Sciences
Zixuan Wang: Chinese Academy of Sciences
Chunchun Zhu: Chinese Academy of Sciences
Hongyan Deng: Chinese Academy of Sciences
Xueyi Sun: Chinese Academy of Sciences
Guangqing Yu: Chinese Academy of Sciences
Fangjing Rong: Chinese Academy of Sciences
Xiaoyun Chen: Chinese Academy of Sciences
Qian Liao: Chinese Academy of Sciences
Shuke Jia: Chinese Academy of Sciences
Wen Liu: Chinese Academy of Sciences
Huangyuan Zha: Chinese Academy of Sciences
Sijia Fan: Chinese Academy of Sciences
Xiaolian Cai: Chinese Academy of Sciences
Jian-Fang Gui: Chinese Academy of Sciences
Wuhan Xiao: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, hypoxic conditions repress antiviral-responsive genes independently of HIF signaling. EGLN1 is identified as a key mediator of the oxygen enhancement of antiviral innate immune responses. Under sufficient oxygen conditions, EGLN1 retains its prolyl hydroxylase activity to catalyze the hydroxylation of IRF3 at proline 10. This modification enhances IRF3 phosphorylation, dimerization and nuclear translocation, leading to subsequent IRF3 activation. Furthermore, mice and zebrafish with Egln1 deletion, treatment with the EGLN inhibitor FG4592, or mice carrying an Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct link between oxygen and antiviral responses, but also provide insight into the mechanisms by which oxygen regulates innate immunity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47814-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47814-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47814-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().