SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity

Area of Science:

• Virology
• Cell Biology
• Structural Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host cell organelles for efficient virion assembly.
• The precise mechanisms by which SARS-CoV-2 hijacks cellular machinery remain incompletely understood.

Purpose of the Study:

• To identify and characterize novel SARS-CoV-2-induced membrane structures involved in viral assembly.
• To elucidate the role of these structures in regulating viral protein processing and infectivity.

Main Methods:

• Electron microscopy to visualize novel membrane structures.
• Protein interaction studies to identify components of the identified structures.
• Viral infection assays to assess the impact of structural disruption on infectivity.

Main Results:

• Identification of the 3a dense body (3DB), an electron-dense structure formed by the SARS-CoV-2 ORF3a protein.
• 3DB formation involves remodeling of the trans-Golgi network and early endosomal membranes.
• 3DBs recruit viral spike (S) and membrane (M) proteins, regulating S protein processing crucial for virion assembly.
• Disruption of 3DB formation significantly reduces viral entry efficiency.

Conclusions:

• The 3a dense body (3DB) is a critical SARS-CoV-2-induced organelle for efficient virion assembly and infectivity.
• 3DBs play a key role in maintaining the optimal spike protein processing required for viral entry.
• Targeting 3DB formation presents a potential therapeutic strategy against SARS-CoV-2 infection.