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.
Chams
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Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, Toulouse, France.
Bonnafous
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Stegmann
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D000818:Animals; D002642:Chick Embryo; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014759:Viral Envelope Proteins; D011092:Polyethylene Glycols