Delivery of Foreign Substances to Cells Mediated by Fusion-Active Reconstituted Influenza Virus Envelopes (Virosomes)

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Abstract
This paper presents a survey of the properties and applications of reconstituted influenza virus envelopes (virosomes). Influenza virosomes can be reconstituted from the original viral membrane lipids and spike glycoproteins, after solubilization of intact virus with octaethyleneglycol monododecyl ether (C12E8) and removal of this detergent with a hydrophobic resin (BioBeads SM-2). These virosomes are functionally active, i.e their membrane fusion activity closely mimics the well-defined low-pH-dependent membrane fusion activity of the intact virus, which is solely mediated by the viral hemagglutinin (HA). By virtue of their fusion activity, virosomes represent a powerful carrier system for cellular delivery of foreign substances, encapsulated in their aqueous interior or co-reconstituted in their membranes. Delivery of an encapsulated, water-soluble, compound is illustrated with data on the toxin gelonin. Protein synthesis in BHK-21 cells in culture is efficiently inhibited when gelonin-containing virosomes fuse from within endosomes, after internalization via receptor-mediated endocytosis, or are induced to fuse with the plasma membrane by a transient lowering of the pH in the medium. The results indicate that delivery is quite efficient; as much as 6 × 103 molecules of gelonin can readily be delivered to the cytoplasm of a single cell by fusion with gelonin-containing virosomes.