Abstract
SV-201, a peptide derived from a conserved and potentially amphipathic region (amino acids 201-229) in the Sendai virus ectodomain, specifically inhibited virus-mediated hemolysis only when added to virions prior to their attachment to red blood cells. Sendai virus-mediated hemagglutinin 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 peptide neutral, was biologically inactive. A second mutant with 7 amino acids randomized at the N terminus keeping the hydrophobicity of the peptide unaltered was only slightly active. A hydrophobic peptide corresponding to the fusion peptide domain was also inactive. SV-201, the two mutants, and the fusion peptide bind similarly with high affinity to both negatively charged phosphatidylserine/phosphatidylcholine and zwitterionic phosphatidylcholine lipid vesicles, suggesting that the inhibitory 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 located in the region corresponding to amino acids 201-229 of the Sendai virus fusion protein. The data presented here suggest that SV-201 disturbs 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 corresponding viruses.
Highlights
Penetration of enveloped viruses into host cells involves the fusion of viral and cellular membranes and the subsequent transfer of genetic material into the target cell [1,2,3]
Synthesis, biological function, and possible site of action of a 29-residue peptide, designated SV-201, derived from a conserved region in the ectodomain of Sendai virus fusion protein
A Shiffer and Edmundson wheel projection of the 18 most conserved amino acids of SV-201 reveals that the peptide has the potential to form an amphipathic ␣-helical structure (Fig. 2, inner circle), in which most of the hydrophobic amino acids are segregated on one surface with
Summary
This may indicate that additional regions may be involved with the membrane fusion process To study this possibility, we selected SV-201 (amino acids 201–229), a domain with intermediate hydrophobicity, preceding the N-terminal heptad repeat and which potentially can form an amphipathic ␣-helix structure. Both the wild type and mutant peptides could not inhibit virus-mediated agglutination of human red blood cells These results, together with data obtained using fluorescently labeled wild type and mutant peptides, are discussed in terms of the possible role of the SV-201 domain of the Sendai virus fusion protein in the assembly of the fusion protein during the initial step of the fusion process and in membrane apposition
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