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A global lipid map defines a network essential for Zika virus replication

Author

Listed:
  • Hans C. Leier

    (Oregon Health & Science University (OHSU))

  • Jules B. Weinstein

    (Oregon Health & Science University (OHSU))

  • Jennifer E. Kyle

    (Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL))

  • Joon-Yong Lee

    (Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL))

  • Lisa M. Bramer

    (Computing and Analytics Division, National Security Directorate, PNNL)

  • Kelly G. Stratton

    (Computing and Analytics Division, National Security Directorate, PNNL)

  • Douglas Kempthorne

    (Oregon Health & Science University (OHSU)
    Center for Diversity and Inclusion, OHSU)

  • Aaron R. Navratil

    (University of California San Diego School of Medicine)

  • Endale G. Tafesse

    (University of Saskatchewan)

  • Thorsten Hornemann

    (University of Zurich)

  • William B. Messer

    (Oregon Health & Science University (OHSU)
    Division of Infectious Diseases, OHSU)

  • Edward A. Dennis

    (University of California San Diego School of Medicine)

  • Thomas O. Metz

    (Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL))

  • Eric Barklis

    (Oregon Health & Science University (OHSU))

  • Fikadu G. Tafesse

    (Oregon Health & Science University (OHSU))

Abstract

Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection.

Suggested Citation

  • Hans C. Leier & Jules B. Weinstein & Jennifer E. Kyle & Joon-Yong Lee & Lisa M. Bramer & Kelly G. Stratton & Douglas Kempthorne & Aaron R. Navratil & Endale G. Tafesse & Thorsten Hornemann & William B, 2020. "A global lipid map defines a network essential for Zika virus replication," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17433-9
    DOI: 10.1038/s41467-020-17433-9
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    Cited by:

    1. Scotland E. Farley & Jennifer E. Kyle & Hans C. Leier & Lisa M. Bramer & Jules B. Weinstein & Timothy A. Bates & Joon-Yong Lee & Thomas O. Metz & Carsten Schultz & Fikadu G. Tafesse, 2022. "A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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