| Autor: |
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, Wuhan Xiao |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-21 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-47814-3 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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