Proc. Natl. Acad. Sci. USA, published online 18 July 2011, doi:10.1073/pnas.1109796108

Infection of human fibroblast cells with the enveloped virus human cytomegalovirus (HCMV) upregulates various components of central carbon metabolism, including fatty acids. Using a lipidomics approach, Liu et al. now show that, in addition to specific glycerophospholipid changes, virion membranes acquire a unique profile that hints at their origin beyond their assembly in a virus-induced organelle. The authors monitored 146 unique glycerophospholipids, including phosphatidic acid (PA) species, phosphatidylethanolamines (PEs) and plasmalogens, over the course of the HMCV replication cycle. They found that the virion glycerophospholipid composition induced by the virus is distinct from that of infected cells and other viral lipidomes that have been studied, including that of HIV-1. However, virion membranes in HCMV-infected cells did resemble those of synaptic vesicles. RNAi knockdown of a critical exocytosis mediator in fibroblasts, SNAP-23, resulted in a severe decrease in HMCV production. These data suggest that HMCV induces and buds into exosome-like vesicles, which are distinct from any existing cellular membrane and which fuse to the plasma membrane of the host cells to release the virions to the extracellular space.