PUBLICATION
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, J.F., Xiao, W.
- ID
- ZDB-PUB-240428-11
- Date
- 2024
- Source
- Nature communications 15: 35333533 (Journal)
- Registered Authors
- Gui, Jian-Fang, Rong, Fangjing, Xiao, Wuhan
- Keywords
- none
- MeSH Terms
-
- Animals
- HEK293 Cells
- Humans
- Hydroxylation
- Hypoxia-Inducible Factor-Proline Dioxygenases*/genetics
- Hypoxia-Inducible Factor-Proline Dioxygenases*/metabolism
- Immunity, Innate*
- Interferon Regulatory Factor-3*/metabolism
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Oxygen*/metabolism
- Phosphorylation
- Proline*/metabolism
- Signal Transduction
- Zebrafish*
- PubMed
- 38670937 Full text @ Nat. Commun.
Citation
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, J.F., Xiao, W. (2024) Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3. Nature communications. 15:35333533.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping