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Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production.
- Source :
- PLoS Pathogens, Vol 18, Iss 3, p e1010366 (2022)
- Publication Year :
- 2022
- Publisher :
- Public Library of Science (PLoS), 2022.
-
Abstract
- Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Volume :
- 18
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.62667b1001c54e43a392bc797b98d694
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.ppat.1010366