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