Lipidomics identifi es a requirement for peroxisomal function during infl uenza virus replication

Abstract

Infl uenza virus acquires a host-derived lipid envelope during budding, yet a convergent view on the role of host lipid metabolism during infection is lacking. Using a mass spectrometry-based lipidomics approach, we provide a systems-scale perspective on membrane lipid dynamics of infected human lung epithelial cells and purifi ed infl uenza virions. We reveal enrichment of the minor peroxisomederived ether-linked phosphatidylcholines relative to bulk ester-linked phosphatidylcholines in virions as a unique pathogenicity-dependent signature for infl uenza not found in other enveloped viruses. Strikingly, pharmacological and genetic interference with peroxisomal and ether lipid metabolism impaired infl uenza virus production. Further integration of our lipidomics results with published genomics and proteomics data corroborated altered peroxisomal lipid metabolism as a hallmark of infl uenza virus infection in vitro and in vivo. Infl uenza virus may therefore tailor peroxisomal and particularly ether lipid metabolism for effi cient replication. -Tanner, L. B., C. Chng, X. L. Guan, Z. Lei, S. G. Rozen, and M. R. Wenk. Lipidomics identifi es a requirement for peroxisomal function during infl uenza virus replication. J. Lipid Res . 2014 . 55: 1357-1365 . © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.