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Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation

Long Shen1, Penghui Hu1, Yanan Zhang1

  • 1Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

Cell Metabolism
|April 2, 2021
PubMed

Insights

Serine metabolism, specifically phosphoglycerate dehydrogenase (PHGDH), dampens antiviral defenses. Inhibiting PHGDH boosts interferon-beta (IFN-β) production, enhancing innate immunity against viral infections.

Area of Science:

  • Immunometabolism
  • Virology
  • Cellular Biology

Background:

  • Serine metabolism influences oncogenesis and immune cell function.
  • Its role in antiviral innate immunity remains unexplored.

Purpose of the Study:

  • To investigate the contribution of serine metabolism to antiviral innate immunity.
  • To elucidate the mechanisms by which serine metabolism impacts interferon-beta (IFN-β) production.

Main Methods:

  • Studied serine synthesis pathway (SSP) enzyme expression in virus-infected macrophages.
  • Utilized genetic suppression and pharmacological inhibition of phosphoglycerate dehydrogenase (PHGDH).
  • Investigated the impact of serine metabolism on ATP6V0d2, YAP, and the TBK1-IRF3 signaling pathway.

Main Results:

  • Virus infection decreased SSP enzyme expression in macrophages.
  • PHGDH suppression or serine restriction enhanced IFN-β-mediated antiviral immunity in vitro and in vivo.
  • Serine metabolism deficiency increased ATP6V0d2 expression by altering H3K27me3.
  • ATP6V0d2 promoted YAP degradation, relieving the blockade on the TBK1-IRF3 axis and boosting IFN-β production.

Conclusions:

  • Phosphoglycerate dehydrogenase (PHGDH) and serine metabolism play a critical role in suppressing antiviral innate immunity.
  • Targeting serine metabolism presents a potential therapeutic strategy for viral infections.
Keywords:
ATP6V0d2H3K27me3PHGDHSAMYAPantiviralserine metabolism

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