TY - JOUR
T1 - Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga
AU - Ziv, Carmit
AU - Malitsky, Sergey
AU - Othman, Alaa
AU - Ben-Dor, Shifra
AU - Wei, Yu
AU - Zheng, Shuning
AU - Aharoni, Asaph
AU - Hornemann, Thorsten
AU - Vardi, Assaf
N1 - We thank Howard Riezman, Joerg Thomas Hannich, and Andreas Zumbuehl for kindly providing the iso-branched C17-SA standard. This research was supported by the European Research Council Starting Grant (INFOTROPHIC Grant 280991, to A.V.), the Swiss National Science Foundation (Grant 31003A_153390/1, to T.H.), the 7th Framework Program of the European Commission (RESOLVE Project 3057, to T.H.), and the Zurich Center of Integrated Human Physiology, University of Zurich (T.H.). C.Z., S.M., and A.O. contributed equally to this work. C.Z., S.M., A.O., A.A., T.H., and A.V. designed research; C.Z., S.M., A.O., Y.W., and S.Z. performed research; C.Z., S.M., A.O., S.B.-D., Y.W., and S.Z. analyzed data; and C.Z., A.O., T.H., and A.V. wrote the paper.
PY - 2016/3/29
Y1 - 2016/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962113317&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.1523168113
DO - https://doi.org/10.1073/pnas.1523168113
M3 - مقالة
SN - 0027-8424
VL - 113
SP - E1907-E1916
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -