title: Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress.
abstract: Human cytomegalovirus induces and requires fatty acid synthesis. This suggests an essential role for lipidome remodeling in viral replication. We used mass spectrometry to quantify glycerophospholipids in mock-infected and virus-infected fibroblasts, as well as in virions. Although the lipid composition of mock-infected and virus-infected fibroblasts was similar, virions were markedly different. The virion envelope contained twofold more phosphatidylethanolamines and threefold less phosphatidylserines than the host cell. This indicates that the virus buds from a membrane with a different lipid composition from the host cell as a whole. Compared with published datasets, the virion envelope showed the greatest similarity to the synaptic vesicle lipidome. Synaptosome-associated protein of 25 kDa (SNAP-25) is a component of the complex that mediates exocytosis of synaptic vesicles in neurons; and its homolog, SNAP-23, functions in exocytosis in many other cell types. Infection induced the relocation of SNAP-23 to the cytoplasmic viral assembly zone, and knockdown of SNAP-23 inhibited the production of virus. We propose that cytomegalovirus capsids acquire their envelope by budding into vesicles with a lipid composition similar to that of synaptic vesicles, which subsequently fuse with the plasma membrane to release virions from the cell.
authors.affiliation: Department of Molecular Biology, Lewis Thomas Laboratory, University, Princeton, NJ 08544, USA.
authors.forename: Sean T H
authors.initials: ST
authors.lastname: Liu
authors.forename: Ronit
authors.initials: R
authors.lastname: Sharon-Friling
authors.forename: Pavlina
authors.initials: P
authors.lastname: Ivanova
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Milne
authors.forename: David S
authors.initials: DS
authors.lastname: Myers
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
authors.forename: Thomas
authors.initials: T
authors.lastname: Shenk
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D003587:Cytomegalovirus / Q000737:chemistry* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005455:Fluorescent Antibody Technique; D020404:Glycerophospholipids / Q000737:chemistry / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000737:chemistry; D014771:Virion / Q000737:chemistry* / Q000502:physiology; D014779:Virus Replication
chemical_list: D020404:Glycerophospholipids; D008055:Lipids; D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C100493:SNAP23 protein, human; D050600:SNARE Proteins; C050629:viral envelope lipids