@article{dd8df06149e849acbc7adfc7d7624867,
title = "A global lipid map defines a network essential for Zika virus replication",
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.",
author = "Leier, {Hans C.} and Weinstein, {Jules B.} and Kyle, {Jennifer E.} and Lee, {Joon Yong} and Bramer, {Lisa M.} and Stratton, {Kelly G.} and Douglas Kempthorne and Navratil, {Aaron R.} and Tafesse, {Endale G.} and Thorsten Hornemann and Messer, {William B.} and Dennis, {Edward A.} and Metz, {Thomas O.} and Eric Barklis and Tafesse, {Fikadu G.}",
note = "Funding Information: This work was supported by the Collins Medical Trust and NIH grant R21AI133631 (H. C.L., J.B.W., and F.G.T.); NIH grant U19AI106772 and administration supplement 5U19A1106772-05 (J.E.K., K.G.S., J.-Y.L., and T.O.M.); NIH grant R21 AI135537, National Center for Advancing Translational Science CTSA UL1 TR000128, Oregon Clinical and Translational Research Institute (W.B.M.); NIH grants R01GM060170 and 9R01AI152579 (E.B.); NIH grants R01DK105961, U19AI106754, and U54GM069338 (A. R.N. and E.A.D.). Lipidomics analyses were performed at the Pacific Northwest National Laboratory in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the U.S. Department of Energy (DOE) Office of Biological and Environmental Research. Reagents were generously shared by Alec J. Hirsch and Daniel N. Streblow (OHSU Vaccine and Gene Therapy Institute), and by Chris G. Burd (Yale), who provided Eqt-SM-oxGFP. We wish to thank Shandee D. Dixon, Fabian Pott, S. Farley, Ayna Alfadhli, Bettie Kareko, and Zoe C. Lyski (OHSU), Christopher J. Parkins and Jessica L. Smith (OHSU Vaccine and Gene Therapy Institute), and Erika M. Zink (PNNL) for providing technical support; Stefanie K. Petrie, Aurelie Snyder, and Brian Jenkins (OHSU Advanced Light Microscopy Core) for their help in designing and analyzing the confocal microscopy experiments; Lenette L. Lu (University of Texas Southwestern Medical Center) for substantial comments on the paper. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-17433-9",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}