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Cell Rep. 2019 Aug 27;28(9):2386-2396.e5. doi: 10.1016/j.celrep.2019.07.085.

MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses.

Author information

1
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China; Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
2
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China.
3
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
4
MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
5
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China.
6
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: zhongwu@bmi.ac.cn.
7
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China. Electronic address: alli@ncba.ac.cn.
8
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: xduan@ncba.ac.cn.

Abstract

It is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo. Mechanistically, we demonstrate that MAVS O-GlcNAcylation is required for virus-induced MAVS K63-linked ubiquitination, thereby facilitating IRF3 activation and IFNβ production. We further demonstrate that D-glucosamine, a commonly used dietary supplement, effectively protects mice against a range of lethal RNA viruses, including human influenza virus. Our study highlights a critical role of O-GlcNAcylation in regulating host antiviral immunity and validates D-glucosamine as a potential therapeutic for virus infections.

KEYWORDS:

MAVS; O-GlcNAcylation; RNA virus; antiviral immunity; glucosamine; influenza; interferon

PMID:
31461653
DOI:
10.1016/j.celrep.2019.07.085
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