Location: Foreign Animal Disease Research
Project Number: 3022-32000-064-053-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jul 1, 2026
End Date: Jun 30, 2028
Objective:
The overarching objectives of the project are to improve protection of livestock in the USA homeland by elucidating the risks associated with emergence of novel foot-and-mouth disease virus (FMDV) strains through recombination in animal hosts simultaneously infected by multiple virus strains. Specific goals are to determine: 1) Does naturally occurring FMDV recombination in sub-clinically infected host animals increase the persistence- and transmission potential of emergent FMDV strains? 2) Does FMDV recombination occur in African (Cape) buffalo, the wildlife host of FMDV? 3) Characterize clinical manifestations and transmission potential of select emergent FMDV strains from endemic regions in domestic sheep and cattle breeds.
Approach:
The cooperator has already collected numerous animal samples from field-based projects that have been demonstrated to contain field strains of foot-and-mouth disease virus (FMDV). This work will leverage availability of these samples obtained from studies carried out in FMD-endemic regions.
Phase I of the project, will characterize the pathogenesis (disease progression) of FMD in African buffalo infected with multiple strains of FMDV. Stored samples of oropharyngeal fluids and tissues from FMDV-infected African buffalo (acute and persistent, subclinical infections) will be analyzed by routine qRT-PCR and virus isolation to confirm the presence of FMDV. Next generation sequencing will be used to characterize detected FMDV strains and to determine if samples contain any recombinant FMDVs. Bio-imaging techniques, such as immunofluorescence microscopy, will be used to further characterize virus distribution, co-localization, and virus-host interactions. Bioinformatics analysis of sequence data will seek to evaluate associations between apparent viral fitness (persistence) and recombination.
Phase II of the project will consist of evaluating the risk posed to domestic sheep and cattle of the novel FMD viruses isolated from phase I. These are viruses known to cause mild or subclinical disease in their native hosts. The new viruses will be used to conduct in vivo animal studies to assess FMDV virulence and transmissibility. Sheep will be infected via simulated natural exposure systems and monitored to evaluate the occurrence of the clinical and persistent FMD. Samples will be collected to determine extent of virus shedding and within-host evolution of viruses during distinct phases of infection. Transmissibility will be assessed by cohabitating infected sheep with naïve cattle with either direct or indirect contact between animals of the same or different species. These studies will seek to quantify the risk posed by small ruminants, which often have milder clinical manifestations of FMD, as potential sources of outbreaks in cattle holdings.