Location: Foreign Animal Disease ResearchTitle: Analysis of SAT type foot-and-mouth disease virus capsid proteins and the identification of putative amino acid residues in virus stability Author
|Maree, Francois - Onderstepoort Veterinary Institute|
|Blignaut, Belinda - University Of Pretoria|
|De Beer, Tjaart - University Of Pretoria|
|Rieder, Aida - Elizabeth|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2013
Publication Date: 5/22/2013
Publication URL: http://handle.nal.usda.gov/10113/57156
Citation: Maree, F.F., Blignaut, B., De Beer, T.A., Rieder, A.E. 2013. Analysis of SAT type foot-and-mouth disease virus capsid proteins and the identification of putative amino acid residues in virus stability. PLoS One. 8(5):e61612 DOI:10.1371/journal.pone.0061612.
Interpretive Summary: For reasons not well understood the South African Territory (SAT) FMDVs are difficult to adapt to tissue culture and typically render low amounts of stable antigen on formulated vaccines. In this study, we investigated the behavior and characterized SAT virus particles exposed to various environmental conditions. This is the first report that describes the identification of capsid determinants implicated in the stability of SAT viruses. Our findings are relevant as they could aid in the development of improved FMD vaccines, engineered to harbor these particular capsid modifications.
Technical 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 SAT2 and SAT3 virus particles to low pH, mild temperatures or high ionic strength conditions, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious capsids displayed a range of 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 inter-pentamer interface were identified that change protonation states at pH 6.0. Of these the H145 of VP3 is 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.