Related Experiment Video
Updated: Jun 25, 2025
09:26
Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
Published on: June 6, 2025
123
SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity
Stella Hartmann1,2, Lisa Radochonski1,2, Chengjin Ye3
1Department of Microbiology, University of Chicago, Chicago, IL, USA 60637.
Research Square
|May 27, 2024
Summary
Scientists discovered a new SARS-CoV-2 structure, the 3a dense body (3DB), essential for virus assembly and infectivity. Targeting 3DBs could lead to new COVID-19 treatments.
Area of Science:
- Virology
- Cell Biology
- Structural Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes double-membrane vesicles for replication.
- The precise mechanisms of SARS-CoV-2 virion assembly remain incompletely understood.
Purpose of the Study:
- To identify and characterize novel SARS-CoV-2-induced membrane structures involved in virion assembly.
- To elucidate the role of the accessory protein ORF3a in the formation of these structures and their contribution to viral infectivity.
Main Methods:
- Correlated cryo-electron tomography and immunofluorescence microscopy to visualize viral structures.
- Genetic manipulation of SARS-CoV-2 ORF3a to assess the impact on 3DB formation and viral infectivity.
- Analysis of viral structural protein recruitment to 3DBs.
Main Results:
- Identification of the 3a dense body (3DB), a novel electron-dense, dynamic membrane structure formed by SARS-CoV-2 ORF3a.
- 3DB formation hijacks trans-Golgi network and early endosomal membranes, is conserved in related coronaviruses, but lost in SARS-CoV.
- 3DBs recruit spike (S) and membrane (M) proteins, facilitating virion assembly through fusion/fission dynamics.
- ORF3a mutants defective in 3DB formation exhibit significantly reduced viral infectivity.
Conclusions:
- The 3a dense body (3DB) is a critical organelle for efficient SARS-CoV-2 virion assembly.
- ORF3a-mediated 3DB formation is essential for optimal viral infectivity.
- 3DBs represent a promising therapeutic target for developing novel COVID-19 prophylactics and treatments.
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