β-Coronaviruses exploit ESCRT for virion assembly and egress.

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Beta-coronaviruses assemble and exit cells via the lysosomal pathway, but mechanisms remain unclear.
• Understanding coronavirus assembly and egress is crucial for pandemic preparedness.

Purpose of the Study:

• To elucidate the molecular mechanisms of beta-coronavirus virion assembly and egress.
• To identify host factors involved in viral replication.

Main Methods:

• Investigated interactions between viral proteins (N, M) and ESCRT components (TSG101, VPS28).
• Utilized electron microscopy and gene knockdown (TSG101, VPS28, MVB12A, CHMP6, VPS4A) to assess effects on virion assembly and egress.
• Tested the efficacy of a TSG101 antagonist (tenatoprazole) on viral particle production and replication.

Main Results:

• Viral proteins N and M interact with ESCRT components TSG101 and VPS28, respectively.
• TSG101 and VPS28 are essential for early and late stages of virion assembly.
• MVB12A and CHMP6 are critical for virion egress, not assembly.
• Inhibition of ESCRT factors or use of tenatoprazole reduced viral particle production and human coronavirus OC43 replication.

Conclusions:

• Beta-coronaviruses hijack the ESCRT machinery for efficient virion assembly and egress.
• The ESCRT-viral protein interaction interface presents a potential target for broad-spectrum antiviral drug development.