2. Academic Validation
  3. Single particle tracking reveals SARS-CoV-2 regulating and utilizing dynamic filopodia for viral invasion

Single particle tracking reveals SARS-CoV-2 regulating and utilizing dynamic filopodia for viral invasion

  • Sci Bull (Beijing). 2023 Oct 15;68(19):2210-2224. doi: 10.1016/j.scib.2023.08.031.
Yue Zhang 1,  Xiaowei Zhang 2,  Zhongyi Li 3,  Weisong Zhao 4,  Hui Yang 5,  Shuangshuang Zhao 6,  Daijiao Tang 1,  Qian Zhang 6,  Zonghong Li 7,  Huisheng Liu 7,  Haoyu Li 4,  Bo Li 3,  Pekka Lappalainen 8,  Tao Xu 7,  Zongqiang Cui 9,  Yaming Jiu 10
Affiliations

Affiliations

  • 1 Unit 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.
  • 2 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
  • 3 Institute of Biomechanics and Medical Engineering, Applied Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.
  • 4 Innovation Photonics and Imaging Center, School of Instrumentation Science and Engineering, Harbin Institute of Technology, Harbin 150080, China.
  • 5 University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
  • 6 Unit 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.
  • 7 Guangzhou Laboratory, Guangzhou 510005, China.
  • 8 Institute of Biotechnology and Helsinki Institute of Life Science, University of Helsinki, Helsinki 00014, Finland.
  • 9 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China. Electronic address: [email protected].
  • 10 Unit 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. Electronic address: [email protected].
PMID: 37661543 DOI: 10.1016/j.scib.2023.08.031
Abstract

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry mechanism has been explored, little is known about how SARS-CoV-2 regulates the subcellular structural remodeling to invade multiple organs and cell types. Here, we unveil how SARS-CoV-2 boosts and utilizes filopodia to enter the target cells by real-time imaging. Using SARS-CoV-2 single virus-like particle (VLP) tracking in live cells and sparse deconvolution algorithm, we uncover that VLPs utilize filopodia to reach the entry site in two patterns, "surfing" and "grabbing", which avoid the virus from randomly searching on the plasma membrane. Moreover, combining mechanical simulation, we elucidate that the formation of virus-induced filopodia and the retraction speed of filopodia depend on Cytoskeleton dynamics and friction resistance at the substrate surface caused by loading-virus gravity, respectively. Further, we discover that the entry process of SARS-CoV-2 via filopodia depends on Cdc42 activity and actin-associated proteins fascin, formin, and Arp2/3. Together, our results highlight that the spatial-temporal regulation of actin Cytoskeleton by SARS-CoV-2 Infection makes filopodia as a highway for virus entry and potentiates it as an Antiviral target.

Keywords

Actin cytoskeleton; Anti-viral therapy; Filopodia; SARS-CoV-2; Viral invasion.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-12755
    99.96%, Cdc42 GTPase Inhibitor