O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity

Tianliang Li, Xinghui Li, Kuldeep S. Attri, Changhong Liu, Lupeng Li, Laura E. Herring, John M. Asara, Yu L. Lei, Pankaj K. Singh, Chengjiang Gao, Haitao Wen

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage. However, the role of individual glucose metabolic pathways during viral infection remains largely unknown. Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity. Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation. Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge. Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation. Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity. Tiangliang et al. demonstrate that enhanced activation of the hexosamine biosynthesis pathway (HBP) occurs upon vesicular stomatitis virus (VSV) infection. HBP activation subsequently promotes RLR-antiviral immunity via O-linked β-N-acetylglucosamine (O-GlcNAc) signaling. Mechanistically, O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for its ubiquitination and downstream signaling activation.

Original languageEnglish (US)
Pages (from-to)791-803.e6
JournalCell Host and Microbe
Volume24
Issue number6
DOIs
StatePublished - Dec 12 2018

Keywords

  • MAVS
  • O-GlcNAc transferase
  • antiviral immunity
  • glucose metabolism
  • hexosamine biosynthesis pathway (HBP)

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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