Publication - Journal Article A global lipid map defines a network essential for Zika virus replication

https://doi.org/10.1038/s41467-020-17433-9
Journal Article
Nature Communications, vol. 11, iss. 1, 2020
Authors
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, Fikadu G. Tafesse
Abstract
AbstractZika 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.
Projects (1)
Project
NIAID Modeling Host Responses to Understand Severe Human Virus Infections, Multi-Omic Viral Dataset Catalog Collection

Last updated on 2024-02-11T22:41:43+00:00 by LN Anderson PNNL DataHub NIAID Program Project: Modeling Host Responses to Understand Severe Human Virus Infections, Multi-Omic Viral Dataset Catalog Collection Background The National Institute of Allergy and Infectious Diseases (NIAID) "Modeling Host...

Biology
Human Health
Integrative Omics

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English