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Published on: January 12, 2024
Quantitative single-virus tracking for revealing the dynamics of SARS-CoV-2 fusion with plasma membrane
Hao-Yang Liu1, Yusi Hu1, Cong Yu1
1State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin 300071, China.
Abstract:
Viral envelope fusion with the host plasma membrane (PM) for genome release is a hallmark step in the life cycle of many enveloped viruses. This process is regulated by a complex network of biomolecules on the PM, but robust tools to precisely elucidate the dynamic mechanisms of virus-PM fusion events are still lacking. Here, we developed a quantitative single-virus tracking approach based on highly efficient dual-color labelling of viruses and batch trajectory analysis to achieve the spatiotemporal quantification of fusion events. This approach allows us to comprehensively analyze the membrane fusion mechanism utilized by pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the single-virus level and precisely elucidate how the relevant biomolecules synergistically regulate the fusion process. Our results revealed that SARS-CoV-2 may promote the formation of supersaturated clusters of cholesterol to facilitate the initiation of the membrane fusion process and accelerate the viral genome release.
Insights
Researchers developed a new method to track single viruses fusing with host cells. This technique revealed that SARS-CoV-2 uses cholesterol clusters to enhance viral genome release.
Area of Science:
- Virology
- Cell Biology
- Biophysics
Background:
- Viral envelope fusion with host plasma membranes is crucial for enveloped virus replication.
- Existing tools lack the precision to fully understand dynamic virus-host fusion mechanisms.
Purpose of the Study:
- To develop a novel quantitative single-virus tracking approach.
- To elucidate the spatiotemporal dynamics of virus-host plasma membrane fusion.
- To analyze the fusion mechanism of pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Main Methods:
- Developed a quantitative single-virus tracking method using dual-color labeling.
- Employed batch trajectory analysis for spatiotemporal quantification of fusion events.
- Investigated the role of biomolecules in SARS-CoV-2 fusion.
Main Results:
- Successfully quantified virus-plasma membrane fusion events at the single-virus level.
- Elucidated the synergistic regulation of fusion by host biomolecules.
- Identified SARS-CoV-2's potential promotion of cholesterol clusters for fusion initiation.
Conclusions:
- The new tracking approach provides precise insights into virus-host fusion dynamics.
- SARS-CoV-2 utilizes cholesterol-rich domains to facilitate membrane fusion and genome release.
- This study advances our understanding of enveloped virus entry mechanisms.
