title: Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga.
abstract: Marine viruses are the most abundant biological entities in the oceans shaping community structure and nutrient cycling. The interaction between the bloom-forming alga Emiliania huxleyi and its specific large dsDNA virus (EhV) is a major factor determining the fate of carbon in the ocean, thus serving as a key host-pathogen model system. The EhV genome encodes for a set of genes involved in the de novo sphingolipid biosynthesis, not reported in any viral genome to date. We combined detailed lipidomic and biochemical analyses to characterize the functional role of this virus-encoded pathway during lytic viral infection. We identified a major metabolic shift, mediated by differential substrate specificity of virus-encoded serine palmitoyltransferase, a key enzyme of sphingolipid biosynthesis. Consequently, unique viral glycosphingolipids, composed of unusual hydroxylated C17 sphingoid bases (t17:0) were highly enriched in the infected cells, and their synthesis was found to be essential for viral assembly. These findings uncover the biochemical bases of the virus-induced metabolic rewiring of the host sphingolipid biosynthesis during the chemical "arms race" in the ocean.
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Carmit
authors.initials: C
authors.lastname: Ziv
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Sergey
authors.initials: S
authors.lastname: Malitsky
authors.affiliation: Institute for Clinical Chemistry, University Hospital Zurich, 8091 Zurich, Switzerland; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany;
authors.forename: Alaa
authors.identifier: http://orcid.org/0000-0002-0092-5594
authors.initials: A
authors.lastname: Othman
authors.affiliation: Biological Services Unit, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shifra
authors.initials: S
authors.lastname: Ben-Dor
authors.affiliation: Institute for Clinical Chemistry, University Hospital Zurich, 8091 Zurich, Switzerland;
authors.forename: Yu
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Shuning
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Asaph
authors.initials: A
authors.lastname: Aharoni
authors.affiliation: Institute for Clinical Chemistry, University Hospital Zurich, 8091 Zurich, Switzerland;
authors.forename: Thorsten
authors.identifier: http://orcid.org/0000-0002-4218-1087
authors.initials: T
authors.lastname: Hornemann
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel; assaf.vardi@weizmann.ac.il.
authors.forename: Assaf
authors.initials: A
authors.lastname: Vardi
mesh_terms: D004267:DNA Viruses / Q000378:metabolism / Q000472:pathogenicity*; D005068:Eutrophication; D015967:Gene Expression Regulation, Viral; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism; D058087:Haptophyta / Q000821:virology*; D054884:Host-Pathogen Interactions; D006900:Hydroxylation; D010935:Plant Diseases / Q000821:virology; D051102:Serine C-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D013107:Sphingolipids / Q000096:biosynthesis*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006028:Glycosphingolipids; D013107:Sphingolipids; D014764:Viral Proteins; D051102:Serine C-Palmitoyltransferase
keywords: Emiliania huxelyi; algal blooms; marine viruses; serine palmitoyltransferase; sphingolipids