Global Changes Induced by Local Perturbations to the HIV-1 Capsid

Abstract

The HIV-1 capsid is a fullerene cone composed of approximately 1300 copies of a single capsomer protein. After entering the host cell, the capsid uncoats through a process that is still poorly understood, releasing its genome into the host cell and enabling replication. The timing of uncoating is affected by a number of host factors that bind to the capsid and alter its stability. For example, the host factor TRIM5α binds to the capsid, induces premature uncoating and prevents replication, pointing to a potential target for therapeutic intervention. Here we explore the mechanism through which local binding events and point mutations affect the overall stability of the capsid. We approximate the capsid's potential using a coarse grained elastic network model and systematically perturb each residue in the capsomer, evaluating its effect on the global potential. We find that residues along the hexamer-hexamer interface have a strong influence on capsid dynamics, suggesting that this region may be crucial for stability and uncoating.