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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Chlorocebus aethiops
  • Female
  • Glucosamine / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Innate*
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Myeloid Cells / metabolism
  • Myeloid Cells / virology
  • Orthomyxoviridae Infections / immunology*
  • Protein Processing, Post-Translational*
  • Signal Transduction
  • Vero Cells


  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • Interferon-beta
  • Glucosamine