美国杜克大学Kevin D. Welsher团队近期取得重要工作进展，他们通过开发高速3D单病毒跟踪方法，捕获到了病毒与细胞相互作用的起点。该项研究成果2022年11月10日在线发表于《自然—方法学》杂志上。

研究人员提出了一种主动反馈单粒子跟踪方法，同时对活细胞环境进行体积成像，称为3D TrIm。3D TrIm以前所未有的细节捕捉到了感染周期的细胞外阶段。研究人员报道了在病毒与细胞相互作用的早期阶段之前未发现的现象，包括毫秒级的掠过接触事件、结合时扩散系数的数量级变化以及沿着细胞突起的圆柱形和线性扩散模式。最后，研究人员演示了利用该方法通过追踪紧密堆积上皮细胞中的单个病毒粒子，将单粒子追踪从简单的单层培养移向更像组织的条件。这种多分辨率方法为捕捉生物系统中的快速三维过程提供了机会。

据介绍，由于病毒粒子在细胞外空间中的快速扩散和所涉及的大型三维细胞结构，病毒与细胞相互作用的早期阶段长期以来一直无法通过现有的显微镜方法进行观察。

附：英文原文

Title: Capturing the start point of the virus–cell interaction with high-speed 3D single-virus tracking

Author: Johnson, Courtney, Exell, Jack, Lin, Yuxin, Aguilar, Jonathan, Welsher, Kevin D.

Issue&Volume: 2022-11-10

Abstract: The early stages of the virus–cell interaction have long evaded observation by existing microscopy methods due to the rapid diffusion of virions in the extracellular space and the large three-dimensional cellular structures involved. Here we present an active-feedback single-particle tracking method with simultaneous volumetric imaging of the live cell environment called 3D-TrIm to address this knowledge gap. 3D-TrIm captures the extracellular phase of the infectious cycle in what we believe is unprecedented detail. We report what are, to our knowledge, previously unobserved phenomena in the early stages of the virus–cell interaction, including skimming contact events at the millisecond timescale, orders of magnitude change in diffusion coefficient upon binding and cylindrical and linear diffusion modes along cellular protrusions. Finally, we demonstrate how this method can move single-particle tracking from simple monolayer culture toward more tissue-like conditions by tracking single virions in tightly packed epithelial cells. This multiresolution method presents opportunities for capturing fast, three-dimensional processes in biological systems.

DOI: 10.1038/s41592-022-01672-3

Source: https://www.nature.com/articles/s41592-022-01672-3