TitleSynaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress.
Publication TypeJournal Article
Year of Publication2011
AuthorsLiu, STH, Sharon-Friling, R, Ivanova, P, Milne, SB, Myers, DS, Rabinowitz, JD, H Brown, A, Shenk, T
JournalProc Natl Acad Sci U S A
Date Published2011 Aug 2
KeywordsBlotting, Western, Cell Line, Cells, Cultured, Chromatography, Liquid, Cytomegalovirus, Fibroblasts, Fluorescent Antibody Technique, Glycerophospholipids, Host-Pathogen Interactions, Humans, Lipids, Male, Mass Spectrometry, Membrane Lipids, Phosphatidylethanolamines, Phosphatidylserines, Qb-SNARE Proteins, Qc-SNARE Proteins, RNA Interference, SNARE Proteins, Synaptic Vesicles, Virion, Virus Replication

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.