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

A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes
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DOI:
10.1016/j.peptides.2010.07.028
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发表时间:
2010-11-01
期刊:
影响因子:
3
通讯作者:
Ulaeto, D. O.
Ulaeto, D. O.
中科院分区:
医学3区
文献类型:
--
作者:
Dean, R. E.;O'Brien, L. M.;Ulaeto, D. O.

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抗菌肽具有抗多种生物膜的活性,是脊椎动物和无脊椎动物系统天然免疫的重要组成部分。这些抗菌肽的作用机制尚不完全清楚,存在许多相互竞争但不一定相互排斥的模型。本研究考察了四种抗菌肽的杀灭病毒活性,人天青素衍生的LL37、非洲爪哇丙氨酸取代的Mainin-2、氨基取代的Mainin-2、Uperin-31和抗痘病毒的Cecropin-LL37杂合体。结果表明,LL37是最有效的抗病毒多肽,但LL37是最有效的,而Uperin-3是密度梯度最小的。经处理的病毒粒子表明,病毒外膜可以被多肽有效地去除,并表明了一种与多肽介导的膜破坏的地毯模型相一致的直接灭活病毒的机制。有趣的是,最不有效的多肽uperin-3 1在诱导中和抗体敏感性方面与其他多肽一样有效。这表明,除了通过基于地毯的机制直接杀死病毒外,这些多肽可能同时运行不同的机制,暴露隔离的抗原而不去除膜(C)2010由Elsevier Inc.发表
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 (C) 2010 Published by Elsevier Inc