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 virusencoded 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.

Host-derived viral transporter protein for nitrogen uptake in infected marine phytoplankton

“…Consistent with the idea that viral proteins act to amend host N metabolic function, a putative glutamine synthetase gene has also been identified in the genomes of NCLDVs such as Mimivirus and Mamavirus (76). These data suggest that viral reprogramming of host N metabolism may be a wider phenomenon (21,77), as has been shown for photosynthetic function (78), sulfur oxidation (79), and lipid (25)(26)(27) and phosphate metabolism (80). Evidence that a viral lineage can acquire host genes to amend host nutrient uptake has implications for our understanding of phytoplankton ecology.…”

“…lipid biosynthesis of eukaryotic algal cells (25)(26)(27). AMGs are thought to modulate host function to improve fitness of the virus and, in some cases, temporarily the host.…”

Marine Prasinoviruses and Their Tiny Plankton Hosts: A Review

“…A key example of this is the acquisition of a coccolithophore host sphingolipid pathway by the coccolithovirus Emiliania huxleyi virus (EhV) [81] to enable a metabolic shift directing sphingolipid synthesis towards virus assembly and infectivity [82]. A number of genes not previously described in viruses are found in prasinovirus genomes.…”

Coccolithoviruses: A Review of Cross-Kingdom Genomic Thievery and Metabolic Thuggery

“…As a result of these studies, considerable insight has been gained regarding (1) the EhV intein [18] and the expression profile of EhV genes during infection [19,20,21]; (2) the EhV life cycle, including its utilization of lipid rafts for budding from the host cells [22,23]; (3) host cellular processes in response to infection such as autophagy and the induction of programmed cell death (PCD) pathways [17,24,25,26,27]; (4) the manipulation of fatty acid and lipid metabolism within infected cells, leading to the production of virus-induced lipids crucial for the progression of the infection [10,28,29,30,31]; (5) vector transmission of EhVs in the natural environment via aerosols and zooplankton faecal pellets [32,33]; and (6) the co-occurring diversity of EhVs and their viruses in a range of habitats, including the Atlantic Ocean, Norwegian Fjords and coastal regions of the Black Sea [8,34,35,36,37,38]. Perhaps the most astonishing finding to date was the identification of a de novo sphingolipid biosynthesis pathway in the EhV genome [1,9,39], encoding virus-derived glycosphingolipids (vGSLs) that are crucial regulators of infection [28].…”