MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses
- Cell Rep. 2019 Aug 27;28(9):2386-2396.e5. doi: 10.1016/j.celrep.2019.07.085.
- 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: [email protected].
- 7. State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China. Electronic address: [email protected].
- 8. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: [email protected].
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.