活细胞中的高密度多色量子点图谱剖析单个多受体病毒相互作用的早期步骤

IF 16 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Nicolas Mateos, Enric Gutierrez-Martinez, Jessica Angulo-Capel, Irene Carlon-Andres, Sergi Padilla-Parra, Maria F. Garcia-Parajo* and Juan A. Torreno-Pina*, 
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引用次数: 0

摘要

病毒捕获和进入靶细胞是最终导致病毒感染的第一个关键步骤。了解这些事件对于设计和开发合适的抗病毒药物和/或疫苗至关重要。病毒捕获涉及病毒与靶细胞质膜上特定受体的动态相互作用。在过去几年中,单个病毒追踪已成为评估病毒在活细胞中的实时动态过程及其与特定细胞成分接触情况的有力方法。然而,在相关空间(纳米)和时间(毫秒)尺度上对单个多分子系统进行成像所面临的技术挑战在很大程度上阻碍了在单个水平上对多受体病毒相互作用早期步骤的直接可视化。在这里,我们提出了一种四色高密度量子点时空映射方法,用于捕捉单个类病毒颗粒(VLP)与来自健康供体的原代活免疫细胞膜上三种不同病毒(共)受体之间的实时相互作用。结合定量工具,我们的方法揭示了三种不同(共)受体在病毒接触前存在协调的时空扩散。通过改变单分子定位累积的时间窗口,我们发现这种协调扩散会影响 HIV-1 和 SARS-CoV-2 VLPs 在宿主膜上的停留时间和潜在的病毒传染性。总之,我们的方法为系统分析病毒与宿主相互作用的初始步骤提供了可能,并可轻松用于在单分子水平上研究其他多分子系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early Steps of Individual Multireceptor Viral Interactions Dissected by High-Density, Multicolor Quantum Dot Mapping in Living Cells

Viral capture and entry to target cells are the first crucial steps that ultimately lead to viral infection. Understanding these events is essential toward the design and development of suitable antiviral drugs and/or vaccines. Viral capture involves dynamic interactions of the virus with specific receptors in the plasma membrane of the target cells. In the last years, single virus tracking has emerged as a powerful approach to assess real time dynamics of viral processes in living cells and their engagement with specific cellular components. However, direct visualization of the early steps of multireceptor viral interactions at the single level has been largely impeded by the technical challenges associated with imaging individual multimolecular systems at relevant spatial (nanometer) and temporal (millisecond) scales. Here, we present a four-color, high-density quantum dot spatiotemporal mapping methodology to capture real-time interactions between individual virus-like-particles (VLPs) and three different viral (co-) receptors on the membrane of primary living immune cells derived from healthy donors. Together with quantitative tools, our approach revealed the existence of a coordinated spatiotemporal diffusion of the three different (co)receptors prior to viral engagement. By varying the temporal-windows of cumulated single-molecule localizations, we discovered that such a concerted diffusion impacts on the residence time of HIV-1 and SARS-CoV-2 VLPs on the host membrane and potential viral infectivity. Overall, our methodology offers the possibility for systematic analysis of the initial steps of viral-host interactions and could be easily implemented for the investigation of other multimolecular systems at the single-molecule level.

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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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