Membrane Fusion Activity of Influenza Virus and Reconstituted Viral Envelopes (Virosomes)

Influenza virus enters its host cell through receptor-mediated endocytosis, routing the virus particles into the endosomal cell compartment. Induced by the mildly acidic pH within the endosomes, the viral membrane fuses with the endosomal membrane, resulting in release of the nucleocapsid in the cellular cytoplasm. This fusion process is mediated by the viral spike glycoprotein hemagglutinin (HA), which undergoes a series of conformational changes at low pH, exposing the hydrophobic N-terminus of the HA 2 subunit. Synthetic peptides corresponding to this “fusion peptide” destabilize model membranes by penetration into the lipid bilayer in an α-helical conformation. Reconstituted influenza virus envelopes (virosomes), prepared by a C12E8 detergent solubilization/removal procedure, exhibit fusion characteristics very similar to those of the native virus. These virosomes are a useful model system for the intact virus in studies on viral fusion and cellular entry. In addition, the virosomes provide a promising carrier system for the introduction of biologically active, foreign molecules into living cells.