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单个粒子跟踪揭示了SARS-CoV-2的调节和利用动态的filopodia病毒入侵

Yue Zhang¹, Xiaowei Zhang², Zhongyi Li³

¹Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Science bulletin

|September 4, 2023

概括

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 使用filopodia,细胞突起,作为进入目标细胞的高速公路. 这一发现通过了解SARS-CoV-2的进入机制,揭示了一个新的抗病毒标.

科学领域:

细胞生物学细胞生物学
病毒学病毒学
生物物理学的生物物理.

背景情况:

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染会影响多个器官,但其细胞进入机制和亚细胞结构重塑仍然不完全理解.
了解SARS-CoV-2如何侵入多种细胞类型对于开发有效的抗病毒策略至关重要.

研究的目的:

为了调查filopodia在SARS-CoV-2细胞进入中的作用.
阐明SARS-CoV-2利用和调节filopodia入侵的机制.
根据进入过程中的病毒与宿主相互作用来识别潜在的抗病毒标.

主要方法:

在活细胞中追踪SARS-CoV-2单个病毒样粒子 (VLP) 的实时成像.
高分辨率VLP运动分析的稀疏解卷算法.
机械模拟分析filopodia动态和基质相互作用.
生物化学测试以评估对Cdc42活性和actin相关蛋白质的依赖性.

主要成果:

SARS-CoV-2 VLPs 通过"冲浪"和"抓取"模式利用 filopodia,优化进入地点的定位.
菲洛波迪亚的形成和收缩是由细胞骨动态和基质摩擦阻力调节的.
SARS-CoV-2 通过 filopodia 进入的过程取决于 Cdc42 活性和活性调节剂 (fascin,formin,Arp2/3).

结论:

SARS-CoV-2 活跃地操纵了行为体细胞骨架,以形成和利用 filopodia 作为细胞进入的直接途径.
菲洛波迪亚是SARS-CoV-2入侵的关键"高速公路",突出了它们作为新型抗病毒点的潜力.

关键词:

动氨酸细胞骨动氨酸细胞骨抗病毒疗法是一种抗病毒疗法.菲洛波迪亚 (Filopodia) 是一种类动物.这就是SARS-CoV-2病毒.病毒入侵是一种病毒入侵.

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