A Global Lipid Map Defines a Network Essential for Zika Virus Replication

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jul 23

PMID 32694525

Citations 38

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

Affiliations

Soon will be listed here.

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.

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