Carlson College of Veterinary Medicine

Highlighted Project

International Collaboration to better understand disease epidemics

• "Multi-scale infection dynamics from cells to landscapes: FMD in African buffalo"
  • Principal investigator: Dr. Anne Jolles, professor of epidemiology, Dr. Bree Beechler, assistant professor of research, Dr. Jan Medlock, associate professor in biomedical sciences 
  • Funded by the National Science Foundation

Abstract
Infectious diseases function at several scales: Pathogens reproduce within cells and organs of their hosts, they transmit among individuals and spread across populations. Because pathogens – especially viruses – replicate rapidly and have high mutation rates, they evolve new variants quickly, changing the ways in which they interact with their hosts – from cellular interactions to how they spread on the landscape. Predicting which viral genetic variants will be more harmful to hosts, which will spread widely, and which will persist in their host populations in the long run is a major challenge in infectious disease biology. In this study, researchers from the US, Great Britain and South Africa will collaborate to discover whether the ability of viral variants to spread and persist in host populations can be predicted from the specific ways in which each variant interacts with host cells -- such as variation in viral growth rate, life span and rate of cell destruction. This is important, because viral interactions with host cells can be screened across thousands of variants in laboratory experiments. By contrast, the spread of new variants in host populations can typically only be observed as it is happening in real-time – and at that point the most efficient variants are difficult to control. Identifying dangerous viral variants before they spread could help prevent disease epidemics. 

The team will investigate viral dynamics from genomic to landscape scales using foot-and-mouth disease viruses (FMDVs) 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 address five Aims:

1. Discover patterns of phenotypic differentiation among current and historic FMDV lineages.
2. Evaluate whether viral phenotypic traits measured in vitro predict viral dynamics in live hosts.
3. Explore how within-host viral / immune dynamics translate to FMD dynamics in buffalo herds.
4. Determine how variation among viral strains structures viral diversity at the landscape scale.
5. Characterize genotypes and phenotypes of FMDV strains that caused outbreaks in livestock around the park.
6. Synthesizing across Aims, the team will assess the utility of their modeling framework by testing whether their 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.
    

*Data provided by the Oregon State University Research Office. Unrounded total: $6,973,001. FY 2023 ran from July 2022 through June 2023.