title: Influenza viruses select ordered lipid domains during budding from the plasma membrane.
abstract: During the budding of enveloped viruses from the plasma membrane, the lipids are not randomly incorporated into the envelope, but virions seem to have a lipid composition different from the host membrane. Here, we have analyzed lipid assemblies in three different viruses: fowl plague virus (FPV) from the influenza virus family, vesicular stomatitis virus (VSV), and Semliki Forest virus (SFV). Analysis of detergent extractability of proteins, cholesterol, phosphoglycerolipids, and sphingomyelin in virions showed that FPV contains high amounts of detergent-insoluble complexes, whereas such complexes are largely absent from VSV or SFV. Cholesterol depletion from the viral envelope by methyl-beta-cyclodextrin results in increased solubility of sphingomyelin and of the glycoproteins in the FPV envelope. This biochemical behavior suggests that so-called raft-lipid domains are selectively incorporated into the influenza virus envelope. The "fluidity" of the FPV envelope, as measured by the fluorescence polarization of diphenylhexatriene, was significantly lower than compared with VSV or SFV. Furthermore, influenza virus hemagglutinin incorporated into the envelope of recombinant VSV was largely detergent-soluble, indicating the depletion of raft-lipid assemblies from this membrane. The results provide a model for lipid selectivity during virus budding and support the view of lipid rafts as cholesterol-dependent, ordered domains in biological membranes.
authors.affiliation: Cell Biology Programme, European Molecular Biology Laboratory, Postfach 10 2209, D-69012 Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Scheiffele
authors.forename: A
authors.initials: A
authors.lastname: Rietveld
authors.forename: T
authors.initials: T
authors.lastname: Wilk
authors.forename: K
authors.initials: K
authors.lastname: Simons
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology; D006224:Cricetinae; D003902:Detergents; D005454:Fluorescence Polarization; D009980:Influenza A virus / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D012672:Semliki forest virus / Q000502:physiology*; D012995:Solubility; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*
chemical_list: D003902:Detergents; D008563:Membrane Lipids