Abstract:
Foot-and-mouth disease virus (FMDV) initiates infection by adhering to integrin receptors on target cells, followed by cell
entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to
irreversible dissociation into pentamers, a characteristic linked to reduced vaccine efficacy. In this study, the structural
stability of intra- and inter-serotype chimeric SAT2 and SAT3 virus particles to various conditions including low pH, mild
temperatures or high ionic strength, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious
capsids displayed different sensitivities in a series of low pH buffers, their stability profiles were comparable at high
temperatures or high ionic strength conditions. Recombinant vSAT2 and intra-serotype chimeric viruses were used to map
the amino acid differences in the capsid proteins of viruses with disparate low pH stabilities. Four His residues at the interpentamer
interface were identified that change protonation states at pH 6.0. Of these, the H145 of VP3 appears to be
involved in interactions with A141 in VP3 and K63 in VP2, and may be involved in orientating H142 of VP3 for interaction at
the inter-pentamer interfaces.
