Cell Membrane Derived Platform To Study Virus Binding Kinetics and Diffusion with Single Particle Sensitivity,ACS Infectious Diseases

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Cell Membrane Derived Platform To Study Virus Binding Kinetics and Diffusion with Single Particle Sensitivity
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-04-24 00:00:00 , DOI: 10.1021/acsinfecdis.7b00270
Nadia Peerboom ₁ , Eneas Schmidt ₁ , Edward Trybala ₂ , Stephan Block ₃ , Tomas Bergström ₂ , Hudson P. Pace ₁ , Marta Bally _{1,

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Affiliation

Discovery and development of new antiviral therapies essentially rely on two key factors: an in-depth understanding of the mechanisms involved in viral infection and the development of fast and versatile drug screening platforms. To meet those demands, we present a biosensing platform to probe virus–cell membrane interactions on a single particle level. Our method is based on the formation of supported lipid bilayers from cell membrane material. Using total internal reflection fluorescence microscopy, we report the contribution of viral and cellular components to the interaction kinetics of herpes simplex virus type 1 with the cell membrane. Deletion of glycoprotein C (gC), the main viral attachment glycoprotein, or deletion of heparan sulfate, an attachment factor on the cell membrane, leads to an overall decrease in association of virions to the membrane and faster dissociation from the membrane. In addition to this, we perform binding inhibition studies using the antiviral compound heparin to estimate its IC₅₀ value. Finally, single particle tracking is used to characterize the diffusive behavior of the virus particles on the supported lipid bilayers. Altogether, our results promote this platform as a complement to existing bioanalytical assays, being at the interface between simplified artificial membrane models and live cell experiments.

中文翻译：

细胞膜衍生平台，以单粒子敏感性研究病毒结合动力学和扩散

新抗病毒疗法的发现和开发基本上取决于两个关键因素：对病毒感染所涉及机制的深入了解以及快速通用的药物筛选平台的开发。为了满足这些需求，我们提供了一个生物传感平台，可以在单个粒子水平上探测病毒-细胞膜的相互作用。我们的方法基于从细胞膜材料形成支持的脂质双层。使用全内反射荧光显微镜，我们报告了病毒和细胞成分对1型单纯疱疹病毒与细胞膜相互作用动力学的贡献。主要病毒附着糖蛋白C（gC）的缺失，或硫酸乙酰肝素的缺失，硫酸乙酰肝素是细胞膜上的附着因子，导致病毒体与膜的缔合的总体减少以及与膜的更快解离。除此之外，我们使用抗病毒化合物肝素进行结合抑制研究以评估其IC₅₀值。最后，使用单颗粒跟踪来表征病毒颗粒在支持的脂质双层上的扩散行为。总而言之，我们的结果促进了该平台作为现有生物分析方法的补充，处于简化的人工膜模型与活细胞实验之间的接口。

更新日期：2018-04-24

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