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Research Project: Development of Swine Models for High Consequence-emerging Zoonotic Threats

Location: Research Programs

Project Number: 3022-32000-018-039-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 22, 2023
End Date: Jul 31, 2024

Objective:
To establish maximum containment capabilities for animal studies with livestock species. ARS scientists will partner with other researchers to gain expertise in performing animal challenges studies with infectious agents of potential significant consequence as well as to develop and evaluate protocols for the safe handling of animals in maximum containment. Work will be performed in the BSL-4 laboratories with a focus on pathogens that fall under USDA’s Zoonotic and Emerging Disease mission space. Studies will be prioritized to address unmet public health needs, diagnostic assay and reagent gaps, or to answer questions of significant concern for the USDA mission.

Approach:
Currently, limited work has been performed to determine the potential risk of transmission of viral hemorrhagic fevers to animals including domestic (agricultural, companion), peri-domestic animals (e.g. rodents), and wildlife. Limited studies were performed with filoviruses, including Ebola virus and Reston virus in domestic pigs. Facility constraints restricted these studies and could only be performed in minipigs and/or immature animals. The use of immature animals limits the interpretation of studies and hampers appropriate risk determination and threat characterization. Use of castrated animals prevented evaluation of potential long-term persistence and provides limited insight into the potential consequences for agriculture byproducts of import and export concern. No studies have been published with other filoviruses. Over the last several years there has been an increase in the number of human outbreaks of both Ebola and Marburg viruses. Outbreaks have been detected in areas previously believed to not be at risk for these viruses in countries with no known historical association with these viruses. In addition, data suggests that these positive sense RNA viruses can establish persistence in otherwise asymptomatic or subclinical hosts that may span years. This increase in frequency and geographic distribution raises concerns increased spillover events. The host range of these viruses remains unknown, but bats are suspected to be reservoirs. Pigs have long been suspected of being naturally permissive and experimentally susceptible to Ebola virus, the cause of the West African outbreak that result in the infection of almost 30,000 people with over 11,000 deaths and multiple imported human cases in countries throughout the world, including the United States. 2008 outbreak of Reston virus in the Philippines reinforced pigs are susceptible to these viruses and may have a role in the epidemiology and spillover into human populations. For the studies outlined here, domestic pigs will be challenged with Marburg virus as a pilot study to determine the susceptibility and risk associated with this heavily used, agriculture production species. Animals will be closely monitored for signs of morbidity and mortality and based on observation animals will be euthanized for post-mortem sample collection and characterization of disease pathogenesis and progression. If animals are demonstrated to be permissive to Marburg virus additional animals may be challenged to better refine and characterize the disease course. In addition, and as space and resources allow, pigs may be challenged with other filoviruses that may demonstrate both human public health and agriculture threats. As part of these efforts, NBAF scientists will gain training and experience working with livestock in BSL4. The experience and models will be translated to the BSL4 for work with other high-consequence, zoonotic pathogens, including Nipah and CCHF viruses in relevant species.