Gaussian curvature and the budding kinetics of enveloped viruses

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• Membrane-enveloped virus formation involves capsid protein assembly and plasma membrane budding.
• Virus budding often stalls before release, a phenomenon previously unexplained.
• Recent simulations suggest the stalling originates from the physics of the budding process.

Purpose of the Study:

• To propose a physical explanation for the pausing and stalling observed during enveloped virus budding.
• To investigate the role of neck geometry and curvature in the budding process.
• To develop a continuum theory describing the kinetic barriers in virus budding.

Main Methods:

• Utilizing Brownian dynamics simulations of a coarse-grained model.
• Analyzing the geometrical properties of the budding neck and assembling capsid.
• Developing and applying a continuum theory to model the budding process.
• Comparing theoretical predictions with simulation results.

Main Results:

• Identified a geometrical potential energy barrier during virus budding.
• Demonstrated that this barrier arises from conflicting curvatures between the capsid and the neck region.
• Characterized the stalling as a kinetic phenomenon driven by capsid protein diffusion and incorporation.
• Validated the continuum theory against Brownian dynamics simulations.

Conclusions:

• The pausing and stalling of enveloped virus budding is a kinetic phenomenon governed by neck geometry.
• A curvature mismatch between the assembling capsid and the budding neck creates a significant energy barrier.
• The proposed continuum theory accurately describes the physics underlying stalled virus release.