Kynurenine-3-monooxygenase (KMO) Broadly Inhibits Viral Infections Via Triggering NMDAR/Ca2+ Influx and CaMKII/ IRF3-mediated IFN-β Production

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2022 Mar 2

PMID 35235615

Authors

Jin Zhao

Jiaoshan Chen

Congcong Wang

Yajie Liu

Minchao Li

Yanjun Li

Ruiting Li

Zirong Han

Junjian Wang

Ling Chen

Yuelong Shu

Genhong Cheng

Caijun Sun

Affiliations

Soon will be listed here.

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.

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