Inhibition of ISAV Membrane Fusion by a Peptide Derived from Its Fusion Protein

TL;DR

A synthetic peptide derived from a virus's fusion protein can block the virus's ability to fuse with cell membranes, offering a potential antiviral strategy.

Contribution

A novel peptide is shown to inhibit ISAV membrane fusion through dual mechanisms involving lipid and fusion protein interactions.

Findings

Peptide 303 effectively inhibits ISAV-FP1-mediated membrane fusion.

Peptide 303 interacts with lipid bilayers and directly with ISAV-FP1.

The inhibitory mechanism involves both membrane binding prevention and disruption of fusion peptide activity.

Abstract

Peptides designed to interfere with specific steps of viral infection mechanisms have shown promising antiviral potential. In this study, we investigated the ability of a synthetic peptide (peptide 303), derived from the fusion protein sequence of the Infectious Salmon Anemia Virus (ISAV), to inhibit membrane fusion mediated by the ISAV fusion peptide (ISAV-FP1). To assess this, we employed a model membrane system consisting of large unilamellar vesicles (LUVs) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol. Membrane fusion kinetics were monitored via R18 fluorescence dequenching. Additionally, the interaction of peptide 303 with lipid membranes was evaluated using fluorescence anisotropy measurements. The potential direct interaction between peptide 303 and ISAV-FP1 was further examined through Förster Resonance Energy Transfer (FRET) assays. Our results demonstrate that peptide 303 effectively inhibits ISAV-FP1-mediated membrane fusion. Furthermore, peptide 303 was shown to interact with lipid bilayers and with ISAV-FP1 itself. These findings suggest a dual inhibitory mechanism in which peptide 303 both prevents ISAV-FP1 binding to the membrane and directly interacts with the fusion peptide, thereby disrupting its fusogenic activity.

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