1. Academic Validation
  2. MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses

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.
Nan Song 1 Qi Qi 2 Ruiyuan Cao 3 Bingjie Qin 3 Bo Wang 3 Yuxia Wang 3 Lei Zhao 3 Wei Li 3 Xianli Du 3 Feng Liu 3 Yunzheng Yan 3 Wen Yi 4 Hailu Jiang 3 Tao Li 5 Tao Zhou 5 Hui-Yan Li 5 Qing Xia 5 Xue-Min Zhang 2 Wu Zhong 6 Ai-Ling Li 7 Xiaotao Duan 8
Affiliations

Affiliations

  • 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].
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12588
    99.98%, O-GlcNAcase Inhibitor