Should Virus Capsids Assemble Perfectly? Theory and Observation of Defects

Area of Science:

• Structural biology
• Virology
• Statistical mechanics

Background:

• Published viral capsid models typically show high regularity.
• Environmental fluctuations and genome delivery necessitate capsid disassembly, potentially leading to defects.
• Defective viral structures are observed in simulations and cryo-electron microscopy.

Purpose of the Study:

• To quantify conditions leading to viral capsid structural defects.
• To investigate the population of defective and vacant sites in viral capsids.
• To explore potential strategies for inhibiting viral assembly based on structural defects.

Main Methods:

• Development of a statistical mechanics model incorporating ideal, defective, and vacant sites.
• Analysis of single-particle cryo-electron microscopy (cryo-EM) data.
• Quantification of defect populations under varying affinity parameters.

Main Results:

• A threshold in affinity parameters was identified, below which defective capsids are prevalent.
• Vacancies are common even when defective sites are disallowed.
• Cryo-EM analysis confirmed approximately 15% of observed particles were defective.

Conclusions:

• Structural heterogeneity in viral capsids is likely under-appreciated.
• The presence of defects offers a novel target for antiviral strategies.
• Understanding capsid assembly defects can inform new methods for inhibiting viral replication.