MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses
Nan Song,
Qi Qi,
Ruiyuan Cao,
Bingjie Qin,
Bo Wang,
Yuxia Wang,
Lei Zhao,
Wei Li,
Xianli Du,
Feng Liu,
Yunzheng Yan,
Wen Yi,
Hailu Jiang,
Tao Li,
Tao Zhou,
Hui-yan Li,
Qing Xia,
Xue-min Zhang,
Wu Zhong,
Ai-ling Li,
Xiaotao Duan
Affiliations
Nan Song
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
Qi Qi
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
Ruiyuan Cao
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Bingjie Qin
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Bo Wang
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Yuxia Wang
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Lei Zhao
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Wei Li
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Xianli Du
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Feng Liu
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Yunzheng Yan
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Wen Yi
MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
Hailu Jiang
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Tao Li
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China
Tao Zhou
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China
Hui-yan Li
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China
Qing Xia
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China
Xue-min Zhang
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
Wu Zhong
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; Corresponding author
Ai-ling Li
State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China; Corresponding author
Xiaotao Duan
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; Corresponding author
Summary: 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. : Mitochondrial antiviral-signaling protein (MAVS) plays a key role in host antiviral innate immunity. Song et al. demonstrate that O-GlcNAcylation of MAVS is critical in RNA virus-induced innate immune response and validate D-glucosamine as a potential broad-spectrum antiviral therapeutic. Keywords: MAVS, O-GlcNAcylation, glucosamine, RNA virus, influenza, interferon, antiviral immunity
