21-EEID US-UK Collab: Multi-scale infection dynamics from cells to landscapes: foot-and-mouth disease viruses in African buffalo

In this project we will investigate the dynamics of foot-and-mouth disease viruses (FMDVs) from genomic to landscape scales in their reservoir host, African buffalo. We will develop a suite of mathematical models to describe viral dynamics at different scales (cell-culture; within-host; between-host; and landscape), which will be parameterised and tested using empirical data collected at each scale. Models will be linked across scales by allowing dynamics at the smaller scales to determine parameters for infection processes at larger scales. The limitations of this modular approach will be assessed through identifiability analysis. More specifically, historic and current isolates collected from the buffalo in the Kruger National Park (KNP) in South Africa will be sequenced and a selection of strains will be characterised in vitro. A mathematical model of dynamics in cell culture will be used to assess differences in growth rates among strains. Buffalo will be challenged with a subset of strains and the dynamics of FMDV and immune responses in each animal quantified using a mathematical model. Relationships between the within-host parameters and in vitro traits will be assessed. The challenge experiments will be used to estimate transmission rates for the strains using transmission models and trees inferred from sequence data. These will be incorporated in a within-herd model to predict variation in transmission dynamics amongst the strains and the predictions tested using longitudinal data collected in wild buffalo herds. Data on circulating viral strains and contact patterns among herds will be used to develop a model to predict viral spread in the landscape. Phylodynamic analysis will be used to test predictions of how life history variation among strains defines patterns of viral spread and persistence in the KNP ecosystem.