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

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. Messer, Edward A. Dennis, Thomas O. Metz, Eric Barklis and Fikadu G. Tafesse ()
Additional contact information
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)
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)
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)

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17433-9

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