H. Alex Brown
Principle Investigator; Professor of Pharmacology, Chemistry, and Biochemistry; Associate Director, VICB;
Last active: 2/12/2015

Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress.

Liu ST, Sharon-Friling R, Ivanova P, Milne SB, Myers DS, Rabinowitz JD, Brown HA, Shenk T
Proc Natl Acad Sci U S A. 2011 108 (31): 12869-74

PMID: 21768361 · PMCID: PMC3150939 · DOI:10.1073/pnas.1109796108

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.

MeSH Terms (23)

Blotting, 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

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