The effects of membrane physical properties on the fusion of Sendai virus with human erythrocyte ghosts and liposomes. Analysis of kinetics and extent of fusion.
A number of amphiphiles which raise the bilayer to hexagonal phase transition temperature (TH) of phosphatidylethanolamine (PE) have been shown to inhibit viral fusion. In this study we have further evaluated the mechanism of this inhibition. Several anionic amphiphiles, including cholesterol sulfate, a component of mammalian plasma membranes, lower the final extent of Sendai virus fusion with both human erythrocyte ghosts and liposomes composed of PE and 5% of the ganglioside, GD1a. A cationic amphiphile slightly increased the final extent of fusion. The fusion rate constant is not greatly affected by the presence of as much as 20% cholesterol sulfate or other charged amphiphiles. The zwitterionic amphiphile, cholesterol phosphorylcholine has no effect on the final extent of fusion but it lowers the fusion rate constant. This amphiphile is potent in raising TH. The amphiphile cholesterol hemisuccinate (CHEMS) stabilizes the bilayer relative to the hexagonal phase at neutral pH, while at acidic pH the formation of the hexagonal phase is promoted. When CHEMS is added to vesicles of egg PE containing 5% GD1a, the rate of Sendai virus fusion is little affected at neutral pH but the rate is significantly enhanced at pH 5.0. These results demonstrate that viral fusion can be modulated, in part, by the tendency of the membrane to convert to the hexagonal phase.
Cheetham
J J
JJ
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Nir
S
S
Johnson
E
E
Flanagan
T D
TD
Epand
R M
RM
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002642:Chick Embryo; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D004910:Erythrocyte Membrane / Q000502:physiology* / Q000648:ultrastructure; D005732:Gangliosides; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes; D008561:Membrane Fusion; D010222:Parainfluenza Virus 1, Human / Q000502:physiology* / Q000648:ultrastructure; D010714:Phosphatidylethanolamines; D013329:Structure-Activity Relationship
D005732:Gangliosides; D008051:Lipid Bilayers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C021298:ganglioside, GD1a; D002784:Cholesterol