A tradeoff between enterovirus A71 particle stability and cell entry.

Area of Science:

• Virology
• Structural Biology
• Biophysics

Background:

• Viral capsids balance genome protection with cell entry.
• Enterovirus A71's stability-entry equilibrium is crucial for infection.

Purpose of the Study:

• To investigate the structural basis of the stability-entry equilibrium in enterovirus A71.
• To understand how genetic mutations affect viral particle stability and infection efficiency.

Main Methods:

• Genetic manipulation of enterovirus A71.
• Cryo-electron microscopy (cryo-EM) for structural determination.
• Molecular dynamics (MD) simulations to analyze particle dynamics.

Main Results:

• A single-point mutation yielded a variant with enhanced thermotolerance and reduced cell entry efficiency.
• The thermostable variant exhibits an expanded conformation with increased protein dynamics.
• Intermediate states suggest a sequential uncoating pathway: lipid pocket factor, VP4, then RNA.

Conclusions:

• Genetic perturbation of the enterovirus A71 equilibrium creates a more stable but less infectious particle.
• The expanded conformation and increased dynamics are key to the thermostable phenotype.
• A stepwise uncoating mechanism involving sequential component release is proposed for the variant.