Lysolipids do not inhibit influenza virus fusion by interaction with hemagglutinin.
The interaction of a spin-labeled lysophosphatidylcholine analog with intact and bromelain-treated influenza viruses as well as with the bromelain-solubilized hemagglutinin ectodomain has been studied. The inhibition of fusion of influenza viruses with erythrocytes by the lysophosphatidylcholine analog was similar to that observed for non-labeled lysophosphatidylcholine. Only a weak interaction of the lysophosphatidylcholine analog with the hemagglutinin ectodomain was observed even upon triggering the conformational change of the ectodomain at a low pH. A significant interaction of spin-labeled lysophosphatidylcholine with the hemagglutinin ectodomain of intact viruses was observed neither at neutral nor at low pH, whereas a strong interaction of the lipid analog with the viral lipid bilayer was evident. We suggest that the high number of lipid binding sites of the virus bilayer and their affinity compete efficiently with binding sites of the hemagglutinin ectodomain. We conclude that the inhibition of influenza virus fusion by lysolipids is not mediated by binding to the hemagglutinin ectodomain, preventing its interaction with the target membrane. The results unambiguously argue for an inhibition mechanism based on the action of lysolipid inserted into the lipid bilayer.
Baljinnyam
Bolormaa
B
Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie, Molekulare Biophysik, Invalidenstrasse 42, D-10115 Berlin, Germany.
Schroth-Diez
Britta
B
Korte
Thomas
T
Herrmann
Andreas
A
D001963:Bromelains / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008055:Lipids; D001963:Bromelains