Emerging infectious diseases often result from increased interactions between humans, their livestock, and wild animals. With an integrated One Health approach, we will study Wesselsbron virus (WSLV), a poorly studied flavivirus related Yellow Fever and Zika that infects both humans, rodents and small ruminants. We will investigate the role of sheep and rodents as potential reservoir or amplifying hosts for WSLV. We will also examine antigenic cross-reactivity/protection between WSLV and related flaviviruses to improve specificity of diagnostic tools. The results of this project will provide valuable information about WSLV and related Flaviviruses, contributing to a better pandemic preparedness.