Thermodynamic stability and kinetic control of capsid morphologies in hepatitis B virus

TL;DR

This study models how ionic conditions influence the thermodynamic stability and kinetic assembly pathways of hepatitis B virus capsid morphologies, explaining observed polymorphism and prevalence ratios.

Contribution

It introduces a combined thermodynamic and kinetic model that accounts for salt effects on HBV capsid assembly, aligning with experimental observations.

Findings

Salt alters the stability of capsid morphologies.

The model predicts the prevalence ratios of different capsid types.

Kinetic modeling matches experimental time-dependent ratios.

Abstract

Polymorphism has been observed in viral capsid assembly, demonstrating the ability of identical protein dimers to adopt multiple geometries under the same solution conditions. A well-studied example is the hepatitis B virus (HBV), which forms two stable capsid morphologies both in vivo and in vitro. These capsids differ in diameter, containing either 90 or 120 protein dimers. Experiments have shown that their relative prevalence depends on the ionic conditions of the solution during assembly. We developed a model that incorporates salt effects by altering the intermolecular binding free energy between capsid proteins, thereby shifting the relative thermodynamic stability of the two morphologies. This model reproduces experimental results on the prevalence ratios of the large and small HBV capsids. We also constructed a kinetic model that captures the time-dependent ratio of the two morphologies under subcritical capsid concentrations, consistent with experimental data.