title: Lipidomics identifies a requirement for peroxisomal function during influenza virus replication.
abstract: Influenza 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 purified influenza virions. We reveal enrichment of the minor peroxisome-derived ether-linked phosphatidylcholines relative to bulk ester-linked phosphatidylcholines in virions as a unique pathogenicity-dependent signature for influenza not found in other enveloped viruses. Strikingly, pharmacological and genetic interference with peroxisomal and ether lipid metabolism impaired influenza virus production. Further integration of our lipidomics results with published genomics and proteomics data corroborated altered peroxisomal lipid metabolism as a hallmark of influenza virus infection in vitro and in vivo. Influenza virus may therefore tailor peroxisomal and particularly ether lipid metabolism for efficient replication.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456 NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore 117456.
authors.forename: Lukas Bahati
authors.initials: LB
authors.lastname: Tanner
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Chng
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
authors.forename: Xue Li
authors.initials: XL
authors.lastname: Guan
authors.affiliation: Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore 169857 Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore 169857 Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Zhengdeng
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore 169857 Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore 169857.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Rozen
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456 NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore 117456 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland Department of Biological Sciences, National University of Singapore, Singapore 117597.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
mesh_terms: D000072283:A549 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D020675:Peroxisomes / Q000378:metabolism* / Q000821:virology; D010713:Phosphatidylcholines / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D010713:Phosphatidylcholines
keywords: biochemistry; ether lipids; glycerophospholipids; lipid metabolism; sphingolipids; systems biology