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

Authors :
Liu X
Tang J
Wang Z
Zhu C
Deng H
Sun X
Yu G
Rong F
Chen X
Liao Q
Jia S
Liu W
Zha H
Fan S
Cai X
Gui JF
Xiao W
Source :
Nature communications [Nat Commun] 2024 Apr 26; Vol. 15 (1), pp. 3533. Date of Electronic Publication: 2024 Apr 26.
Publication Year :
2024

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.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
15
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
38670937
Full Text :
https://doi.org/10.1038/s41467-024-47814-3