A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes

• Published in: Peptides (New York, N.Y. : 1980) Vol. 31; no. 11; pp. 1966 - 1972
• Main Authors: Dean, R.E., O’Brien, L.M., Thwaite, J.E., Fox, M.A., Atkins, H., Ulaeto, D.O.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2010
• Subjects: Amides; Animals; Antigens; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptide; Biological; Carpet; Carpets; Cathelicidins - pharmacology; Cecropins - pharmacology; Cell Line; Envelopes; Inactivation; Invertebrates; Magainins; Membrane; Membranes; Peptides; Peptides - pharmacology; Vaccinia virus; Vaccinia virus - drug effects; Virion - drug effects; Xenopus; Xenopus Proteins - pharmacology; Vaccinia virus; Membrane; Carpet; Antimicrobial peptide
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2010.07.028

▶ Peptides attack double-membraned extracellular virions of vaccinia virus. ▶ Peptides remove the outer membrane entirely in a single event. ▶ Peptides expose antigens sequestered beneath the outer membrane. ▶ Direct killing is consistent with a carpet model. Antimicrobial peptides have activity against a wide variety of biological membranes and are an important component of innate immunity in vertebrate as well as invertebrate systems. The mechanisms of action of these peptides are incompletely understood and a number of competing but not necessarily mutually exclusive models exist. In this study we examined the virucidal activity of four peptides, the human cathelicidin derived LL37, Xenopus alanine-substituted Magainin-2 amide, uperin-3.1, and a cecropin-LL37 hybrid against vaccinia virus. The peptides were shown to be differentially virucidal but all were shown to attack the viral envelope, with LL37 being the most effective and uperin-3.1 the least. Density gradient analysis of the treated virions indicated the virus outer membrane was efficiently removed by peptide action and suggests a mechanism of direct virus inactivation that is consistent with the carpet model for peptide-mediated membrane disruption. Interestingly, the least effective peptide uperin-3.1 was equally effective as the others at inducing susceptibility to neutralizing antibody. This suggests that in addition to direct killing by a carpet-based mechanism, the peptides may simultaneously operate a different mechanism that exposes sequestered antigen without membrane removal.