Journal article

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

  • Leier HC Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA.
  • Weinstein JB Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA.
  • Kyle JE Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA, 99352, USA.
  • Lee JY Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA, 99352, USA.
  • Bramer LM Computing and Analytics Division, National Security Directorate, PNNL, Richland, WA, 99352, USA.
  • Stratton KG Computing and Analytics Division, National Security Directorate, PNNL, Richland, WA, 99352, USA.
  • Kempthorne D Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA.
  • Navratil AR Departments of Chemistry & Biochemistry and Pharmacology, University of California San Diego School of Medicine, La Jolla, CA, 92093, USA.
  • Tafesse EG Department of Plant Sciences, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, SK, S7N 5A8, Canada.
  • Hornemann T University Zurich and University Hospital Zurich, University of Zurich, Zurich, 8091, Switzerland.
  • Messer WB Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA.
  • Dennis EA Departments of Chemistry & Biochemistry and Pharmacology, University of California San Diego School of Medicine, La Jolla, CA, 92093, USA.
  • Metz TO Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA, 99352, USA.
  • Barklis E Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA.
  • Tafesse FG Department of Molecular Microbiology & Immunology, Oregon Health & Science University (OHSU), Portland, OR, 97239, USA. tafesse@ohsu.edu.
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  • 2020-07-23
Published in:
  • Nature communications. - 2020
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/30445
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