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Glycerophospholipid remodeling is critical for orthoflavivirus infection

Author

Listed:
  • Julia Hehner

    (University of Marburg)

  • Laura Schneider

    (University of Marburg)

  • Anna Woitalla

    (Research Center Borstel – Leibniz Lung Center)

  • Benjamin Ott

    (Justus Liebig University Giessen)

  • Kim Chi Thi Vu

    (University of Marburg)

  • Anja Schöbel

    (University of Marburg)

  • Torsten Hain

    (Justus Liebig University Giessen)

  • Dominik Schwudke

    (Research Center Borstel – Leibniz Lung Center
    Partner Site Hamburg-Lübeck-Borstel-Riems
    Site Research Center Borstel – Leibniz Lung Center)

  • Eva Herker

    (University of Marburg)

Abstract

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.

Suggested Citation

  • Julia Hehner & Laura Schneider & Anna Woitalla & Benjamin Ott & Kim Chi Thi Vu & Anja Schöbel & Torsten Hain & Dominik Schwudke & Eva Herker, 2024. "Glycerophospholipid remodeling is critical for orthoflavivirus infection," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52979-y
    DOI: 10.1038/s41467-024-52979-y
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    1. Qian Chen & Jordi Gouilly & Yann J. Ferrat & Ana Espino & Quentin Glaziou & Géraldine Cartron & Hicham El Costa & Reem Al-Daccak & Nabila Jabrane-Ferrat, 2020. "Metabolic reprogramming by Zika virus provokes inflammation in human placenta," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Hothorn, Torsten & Hornik, Kurt & van de Wiel, Mark A. & Zeileis, Achim, 2006. "A Lego System for Conditional Inference," The American Statistician, American Statistical Association, vol. 60, pages 257-263, August.
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