A PEPTIDE DERIVED FROM A CONSERVED DOMAIN OF SENDAI VIRUS FUSION PROTEIN INHIBITS VIRUS-CELL FUSION - A PLAUSIBLE MODE OF ACTION

SV-201, a peptide derived from a conserved and potentially amphipathic region (amino acids 201-229) in the Sendai virus ectodomain, specific ally inhibited virus-mediated hemolysis only when added to virions pri or to their attachment to red blood cells. Sendai virus-mediated hemag glutinin assay in the presence of SV-201 demonstrated that the peptide does not disturb the binding of virions to the target red blood cells . A mutated peptide with 2 amino acids substitution, rendering the pep tide neutral, was biologically inactive. A second mutant with 7 amino acids randomized at the N terminus keeping the hydrophobicity of the p eptide unaltered was only slightly active. A hydrophobic peptide corre sponding to the fusion peptide domain was also inactive. SV-201, the t wo mutants, and the fusion peptide bind similarly with high affinity t o both negatively charged phosphatidylserine/phosphatidylcholine and z witterionic phosphatidylcholine lipid vesicles, suggesting that the in hibitory effect is not due merely to membrane modulation. Fluorescence studies with rhodamine-labeled peptides and SV-201-induced inhibition assays, demonstrated that the SV-201 binding site is most probably lo cated in the region corresponding to amino acids 201-229 of the Sendai virus fusion protein. The data presented here suggest that SV-201 dis turbs a functional domain in the Sendai virus fusion protein, which is most probably associated with the assembly of the fusion protein and/ or membrane apposition. The existence of homologous SV-201 regions in other viruses suggests that these regions may have a similar role, and their synthetic counterparts may act as inhibitors for the correspond ing viruses.