Mechanics of diffusion-mediated budding and implications for virus replication and infection

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• Virus replication relies on budding, a process involving membrane protrusion and envelope formation.
• Nucleocapsid-membrane adhesion, driven by transmembrane proteins (TPs), overcomes the energetic barrier of membrane deflection.
• TP diffusion kinetics across the membrane critically influence budding rates.

Purpose of the Study:

• To develop a simple biophysical model for diffusion-mediated virus budding.
• To investigate size limitations and size-dependent kinetics of budding.
• To predict virion size distribution and validate against experimental data for various viruses.

Main Methods:

• Development of a mathematical model for diffusion-mediated budding.
• Analysis of energetic barriers and kinetic factors in bud formation.
• Comparison of model predictions with experimental data for coronavirus, HIV, influenza, hepatitis, and SARS-CoV-2.

Main Results:

• The model predicts an optimal virion radius for the fastest budding kinetics.
• Budding imposes significant size constraints, influencing viral replication and population dynamics.
• Model predictions align with experimental observations for multiple viruses, including size distribution of SARS-CoV-2.

Conclusions:

• Budding kinetics and size limitations are crucial for virus replication and evolution.
• The model provides a framework for understanding virus assembly and infection mechanisms.
• The study highlights the importance of diffusion and membrane interactions in viral egress.