US:UK Collab: Multi-scale infection dynamics from cells to landscapes: FMD in African buffalo

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The goal of this study is to determine if viral spread and persistence can be predicted from viral interactions with host cells. Predicting which viral genetic variant will be more harmful to hosts, which will spread widely, and which will persist in host populations is a major challenge. In this study, researchers from the United States, the United Kingdom, and South Africa will collaborate to investigate the spread of foot-and-moth disease virus (FMDV) in wild African buffalo by studying viral growth rate, life span, and the rate of cell destruction. This information can then be used to screen future variants and identify dangerous variants before they spread. The project will investigate spillover of FMDV into domestic cattle. It will also allow US graduate students and post-doctoral scholars to learn to collaborate internationally with students from the UK and South Africa.The team will investigate viral dynamics from genomic to landscape scales using foot-and-mouth disease viruses in their wildlife host, African buffalo, as a model system. FMDVs are some of the fastest-evolving and most contagious known pathogens, which cause enormous losses when they spillover from wildlife to livestock populations. FMDV variants from Kruger National Park, South Africa, have been collected and archived for over forty years, providing historical and phylogenetic context for evaluating lineages that are currently circulating in the park’s buffalo population. The researchers will create a data-driven mathematical framework linking viral dynamics across organizational scales, to test whether dynamics within hosts, at population and landscape scales, can be predicted from phenotypic variation among viral lineages. Using experiments, observational field studies and mathematical models, the team will: discover patterns of phenotypic differentiation among current and historic FMDV lineages, evaluate whether viral phenotypic traits measured in vitro predict viral dynamics in live hosts, explore how within-host viral and immune dynamics translate to FMD dynamics in buffalo herds, determine how variation among viral strains structures viral diversity at the landscape scale, and characterize genotypes and phenotypes of FMDV strains that caused outbreaks in livestock. The modeling framework will be tested to see whether the approach correctly distinguishes historic lineages that spread, diversified, and in some cases spilled over to livestock, from strains that petered out after modest periods of growth.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.