O- Linked N-Acetylglucosamine Modification of Mitochondrial Antiviral Signaling Protein Regulates Antiviral Signaling by Modulating Its Activity

Front Immunol. 2021 Feb 2:11:589259. doi: 10.3389/fimmu.2020.589259. eCollection 2020.


Post-translational modifications, including O-GlcNAcylation, play fundamental roles in modulating cellular events, including transcription, signal transduction, and immune signaling. Several molecular targets of O-GlcNAcylation associated with pathogen-induced innate immune responses have been identified; however, the direct regulatory mechanisms linking O-GlcNAcylation with antiviral RIG-I-like receptor signaling are not fully understood. In this study, we found that cellular levels of O-GlcNAcylation decline in response to infection with Sendai virus. We identified a heavily O-GlcNAcylated serine-rich region between amino acids 249-257 of the mitochondrial antiviral signaling protein (MAVS); modification at this site disrupts MAVS aggregation and prevents MAVS-mediated activation and signaling. O-GlcNAcylation of the serine-rich region of MAVS also suppresses its interaction with TRAF3; this prevents IRF3 activation and production of interferon-β. Taken together, these results suggest that O-GlcNAcylation of MAVS may be a master regulatory event that promotes host defense against RNA viruses.

Keywords: O-linked N-Acetylglucosamine (O-GlcNAc); RIG-I-like receptors signaling; host defense mechanism; innate immunity; mitochondrial antiviral signaling protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / immunology*
  • Acylation
  • Adaptor Proteins, Signal Transducing / immunology*
  • Cell Line
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate
  • Mitochondria / immunology
  • Respirovirus Infections / immunology*
  • Sendai virus*
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • MAVS protein, human
  • Acetylglucosamine