Inhibition of influenza-induced membrane fusion by lysophosphatidylcholine.
Lysolipids have been reported to inhibit various membrane fusion events, and it was suggested that inhibition was due to their "inverted cone" shape, which hinders the formation of intermediate lipid structures required for fusion (Chernomordik, L. V., Vogel, S. S., Sokoloff, A., Onaran, H. O., Leikina, E. A., and Zimmerberg, J. (1993) FEBS Lett. 318, 71-76). Here, the effect of lysophosphatidylcholine (LPC) on fusion mediated by the hemagglutinin (HA) of influenza virus was investigated. Virus-liposome fusion was inhibited by LPC if the lysolipid was added to the membranes from an aqueous stock solution but not if LPC was symmetrically distributed over both leaflets of the liposomal bilayer. These findings would be consistent with an effect of LPC on lipid intermediate formation, but inhibition increased with increasing acyl chain length and thus a less pronounced inverted cone shape of the lysolipids suggesting that the mechanism of inhibition might be different. At low pH, due to the exposure of the fusion peptide of HA, followed by its insertion into the liposomal membrane, virus acquires the ability to bind to zwitterionic liposomes lacking receptors for HA. This type of binding was inhibited by LPC. Moreover, leakage of calcein from receptor-containing liposomes, induced by purified HA at low pH, was inhibited by LPC. Therefore, the inhibition of influenza-induced fusion by LPC was caused by the binding of LPC to fusion peptides, thereby preventing their interaction with the target membrane rather than an effect on intermediate lipid structures.
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008561:Membrane Fusion / Q000187:drug effects*; D009975:Orthomyxoviridae / Q000187:drug effects*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008081:Liposomes; D008244:Lysophosphatidylcholines