Influenza hemagglutinin mediated fusion of membranes containing poly(ethylene-glycol) grafted lipids: new insights into the fusion mechanism.

The influence of a hydrophilic layer covering the membrane on influenza hemagglutinin (HA) mediated fusion was investigated using membranes containing poly(ethylene-glycol) grafted phosphatidylethanolamine (PEG-2000-PE). Steric inhibition of HA-membrane interactions by these lipids affected virus fusion (half-maximal inhibition at 0.8 mol% for lipids with 114 ethylene glycol residues, or at 3.2 mol% for 45 residues (PEG-2000-PE), concentrations at which the PEG moieties adopt a random coil structure). Reconstituted viral membranes containing 3 mol% PEG-2000-PE retained 40% of their fusion activity. Therefore, efficient fusion is possible with membranes completely covered by a hydrophilic layer of several nanometers, and fusogenic virosomes containing PEG-PE are feasible.