Specific interactions between envelope and core proteins govern the membrane assembly of most enveloped viruses. Despite this, mixed infections lead to pseudotyping, the association of the viral cores of one virus with the envelopes of another. How does this occur? We show here that the detergent-insoluble lipid rafts of the plasma membrane function as a natural meeting point for the transmembrane and core components of a phylogenetically diverse collection of enveloped viruses. As a result, viral particles preferentially incorporate both the envelope components of other viruses as well as the extra- and intracellular constituents of host cell Lipid rafts, including gangliosides, glycosyl phosphatidylinositol-anchored surface proteins, and intracellular signal transduction molecules. Pharmacological disruption of lipid rafts interferes with virus production.
