title: Peptide inhibitors of enveloped virus infection inhibit phospholipid vesicle fusion and Sendai virus fusion with phospholipid vesicles.
abstract: Small hydrophobic peptides that are capable of inhibiting Sendai virus infection of cells (Richardson, C. D., Scheid, A., and Choppin, P. W. (1980) Virology 105, 205-222) are also capable of inhibiting membrane fusion in a pure lipid vesicle system. Large unilamellar vesicles of N-methyl dioleoylphosphatidylethanolamine containing encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid and/or p-xylene bis (pyridinium bromide) were formed by extrusion. Vesicle fusion (contents mixing) and leakage were then monitored with the 1-aminonaphthalene-3,6,8-trisulfonic acid/p-xylene bis(pyridinium bromide) fluorescence assay. Sendai virus fusion with lipid vesicles was measured by following the relief of fluorescence quenching of virus labeled with octadecylrhodamine B chloride, a lipid mixing assay for fusion. The efficiency with which the peptides carbobenzoxy-D-Phe-L-PheGly, carbobenzoxy-L-Phe-L-Tyr, and carbobenz-oxy-Gly-L-Phe inhibit fusion of N-methyl dioleoyl-phosphatidylethanolamine large unilamellar vesicles directly paralleled their previously known effectiveness in blocking virus infectivity of cultured cells. In addition, above a certain concentration threshold, the inhibitory peptides decreased the initial rate of leakage from lipid vesicles. The inhibition by these peptides of virus-vesicle fusion followed the same order of potency as for vesicle-vesicle fusion. The observation of the same relative potency of these peptides toward inhibition of virus-cell infection, and virus-vesicle and vesicle-vesicle membrane fusion suggested that these peptides inhibited virus-cell infection by inhibiting the ability of the virus to fuse with the cell. Furthermore, these results suggest that the mechanism of inhibition of all three fusion events may have steps in common.
authors.affiliation: Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
authors.forename: D R
authors.initials: DR
authors.lastname: Kelsey
authors.forename: T D
authors.initials: TD
authors.lastname: Flanagan
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: P L
authors.initials: PL
authors.lastname: Yeagle
mesh_terms: D000595:Amino Acid Sequence; D066298:In Vitro Techniques; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human; D010455:Peptides / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000502:physiology*
chemical_list: D010455:Peptides; D014760:Viral Fusion Proteins