Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-021-027-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jul 1, 2026
End Date: Jun 30, 2028
Objective:
Accidental importation, natural introduction, or intentional release of zoonotic, emerging, or exotic viruses poses a continuing threat to United States agriculture, livestock health, food security, agricultural trade, and public health. The ability to evaluate these pathogens in relevant agricultural species is a core component of preparedness for the Agricultural Research Service, the National Bio and Agro-Defense Facility (NBAF), and the Zoonotic and Emerging Disease Research Unit (ZEDRU). The objective of this collaborative project is to assess the susceptibility of agricultural animals to selected zoonotic, emerging, or exotic viruses and to characterize disease progression, transmission potential, and agricultural impact in appropriate animal models. The project will support development and refinement of animal models that can be used to evaluate pathogenesis, diagnostic approaches, medical countermeasures, and risk to United States livestock systems. Specific objectives are to: Establish risk profiles for selected zoonotic, emerging, or exotic viruses in agricultural species, including small ruminants, swine, and other relevant livestock or model species. Evaluate disease progression, clinical outcomes, tissue distribution, viral shedding, immune responses, and potential transmission following experimental exposure to selected viruses. Develop and characterize a Nairobi sheep disease virus model in sheep as both an agricultural disease model and a surrogate system to inform future work with related high-consequence orthonairoviruses, including Crimean-Congo hemorrhagic fever virus. Compare findings from Nairobi sheep disease virus studies with data generated through related collaborative studies on Crimean-Congo hemorrhagic fever virus, as appropriate, to improve understanding of orthonairovirus disease progression and host responses in agricultural animals. Evaluate the potential risk of newly identified or poorly characterized viruses detected through ecological and One Health surveillance studies, including novel paramyxoviruses, Cedar virus or related viruses, bat-associated reoviruses, or other candidate viruses identified at bat-swine-human interfaces. Generate animal model data, protocols, and risk information that can support future transfer of appropriate models, methods, and capabilities to the National Bio and Agro-Defense Facility when operational. Strengthen United States Department of Agriculture preparedness by identifying emerging or exotic viral threats that could affect American livestock, agricultural markets, and national biosecurity.
Approach:
The Cooperator and ARS will collaborate to evaluate disease progression and agricultural risk associated with selected zoonotic, emerging, or exotic viruses. The project will use relevant small and large animal models to assess susceptibility, pathogenesis, clinical disease, viral replication, viral shedding, tissue distribution, immune responses, and potential transmission in agricultural species. Experimental designs will be based on virus biology, relevance to United States agriculture, animal species at risk, availability of virus stocks, institutional approvals, containment requirements, and animal housing capacity. Initial studies will focus on Nairobi sheep disease virus, an orthonairovirus that causes disease in small ruminants and is relevant to agricultural preparedness. Sheep will be experimentally exposed to Nairobi sheep disease virus under approved biocontainment conditions to characterize disease course, clinical signs, pathology, viral load, tissue tropism, shedding, and host immune responses. These studies will support development of a disease model for an exotic tick-borne virus of agricultural concern and provide a surrogate model to inform future studies with related high-consequence orthonairoviruses.Nairobi sheep disease virus was selected because of its relevance to livestock health, its relationship to Crimean-Congo hemorrhagic fever virus, and concerns associated with the movement or establishment of competent tick vectors. Crimean-Congo hemorrhagic fever virus is a Biosafety Level 4 pathogen and a priority agent for future work at the National Bio and Agro-Defense Facility once fully operational. Data from Nairobi sheep disease virus studies will be compared, as appropriate, with data from related collaborative studies on Crimean-Congo hemorrhagic fever virus conducted through an international research partnership and associated subaward. This comparison will help identify disease features, host responses, and model endpoints useful for future high-containment studies.The project will also support evaluation of selected viruses identified through ongoing ecological and One Health surveillance at interfaces where bats, swine, and people overlap. Candidate viruses may include Cedar virus or related paramyxoviruses, novel paramyxoviruses, bat-associated reoviruses, or other emerging viruses detected through field investigations. Final virus selection will be based on available surveillance data, evidence of zoonotic or livestock relevance, virus stock availability and quality, biosafety and biosecurity requirements, institutional approvals, and access to appropriate animal facilities. For swine model development, selected candidate viruses will be evaluated in pigs when scientific rationale, approvals, virus availability, and animal space allow. Studies may assess clinical disease, viral replication, shedding, tissue distribution, immune responses, and transmission potential. If large animal space is limited, pilot studies may be conducted in suitable small animal models to inform dose, exposure route, sampling schedules, biosafety practices, and feasibility before advancing to livestock studies.