Abstract：
The interactions of viral fusion peptides from influenza (E4K and Ac-E4K) and human immunodeficiency virus (gp41 and Ac-gp41) with planar lipid bilayers and monolayers was investigated herein. A combination of surface-sensitive techniques, including quartz crystal microbalance with dissipation (QCM-D), Langmuir-Blodgett area-pressure isotherms with Micro-Brewster angle microscopy, and neutron reflectometry, was employed. Differences in the interactions of the viral fusion peptides with lipid bilayers featuring ordered and disordered phases, as well as lipid rafts, were revealed. The HIV fusion peptide (gp41) exhibited strong binding to the DOPC/DOPS bilayer, comprising a liquid disordered phase, with neutron reflectometry (NR) showing interaction with the bilayer\'s headgroup area. Conversely, negligible binding was observed with lipid bilayers in a liquid ordered phase. Notably, the influenza peptide (E4K) demonstrated slower binding kinetics with DOPC/DOPS bilayers and distinct interactions compared to gp41, as observed through QCM-D. This suggests different mechanisms of interaction with the lipid bilayers: one peptide interacts more within the headgroup region, while the other is more involved in transmembrane interactions. These findings hold implications for understanding viral fusion mechanisms and developing antimicrobials and antivirals targeting membrane interactions. The differential binding behaviours of the viral fusion peptides underscore the importance of considering membrane composition and properties in therapeutic strategy design.
摘要：
本文研究了来自流感的病毒融合肽（E4K和Ac-E4K）和人类免疫缺陷病毒（gp41和Ac-gp41）与平面脂质双层和单层的相互作用。表面敏感技术的组合，包括石英晶体微天平（QCM-D），使用Micro-Brewster角度显微镜的Langmuir-Blodgett区域压力等温线，和中子反射计，被雇用。病毒融合肽与脂质双层相互作用的差异具有有序和无序的相，以及脂筏，被揭露。HIV融合肽（gp41）表现出与DOPC/DOPS双层的强结合，包含一个无序的液相，中子反射仪(NR)显示与双层头群区域的相互作用。相反，在液体有序相中的脂质双层观察到可忽略的结合。值得注意的是,通过QCM-D观察到，与gp41相比，流感肽（E4K）与DOPC/DOPS双层的结合动力学较慢，相互作用明显。这表明与脂质双层相互作用的不同机制：一种肽在头基区域内相互作用更多，而另一种则更多地参与跨膜相互作用。这些发现对于理解病毒融合机制和开发靶向膜相互作用的抗微生物剂和抗病毒剂具有重要意义。病毒融合肽的差异结合行为强调了在治疗策略设计中考虑膜组成和性质的重要性。
