Location: Virus and Prion Research
Project Number: 5030-32000-230-000-D
Project Type: In-House Appropriated
Start Date: Oct 5, 2021
End Date: Oct 4, 2026
Objective 1. Elucidate the molecular mechanisms of PRRSV immunity. 1.A. Characterize virus-host interactions and determine innate and adaptive immune pathways that contribute to PRRSV disease susceptibility or immunity to inform the development of highly effective vaccines against very virulent strains. 1.B. Define mechanisms of immune evasion that contribute to PRRSV disease pathogenicity, and which can be targeted through recombinant vaccines to improve vaccine efficacy. Objective 2. Develop countermeasures to detect, prevent, and control endemic and emerging porcine coronaviruses. 2.A. Identify and characterize factors that determine coronavirus tissue and cellular tropism and adaptation to swine hosts. 2.A.2. Identify and characterize factors that determine coronavirus tissue and cellular tropism and adaptation to swine hosts. 2.B. Investigate and develop vaccine platforms that induce broadly cross-protective immune responses against PEDV, override PEDV vaccine interference from passively acquired immunity, and rapidly adapt to new and emerging porcine coronaviruses. 2.C. Determine genomic factors that drive coronavirus evolution and the mechanisms that lead to the emergence and spread of new porcine coronavirus strains. Objective 3. Predict and characterize the ecology and evolution of emerging viral diseases of swine. 3.A. Identify viral genes with mutations that are associated with SVA virulent and attenuated field strains and determine mechanisms of viral pathogenesis. 3.B. Conduct the molecular characterization of emerging SVA, including phylogenetic network analysis of viruses circulating in North America and Asia to predict the evolution of new SVA strains. 3.C. Develop SVA swine laboratory models to inform the development of vaccines. 3.D. Evaluate SVA new vaccine platforms and determine whether vaccines against SVA will cross-react with FMDV or interfere with FMDV serological surveillance. 3.E. Develop methods to rapidly detect and characterize the etiology of new and emerging viruses that may have an impact on swine health.
This research project will focus on swine diseases caused by viruses that are top concerns for United States pork producers: porcine reproductive and respiratory syndrome, porcine coronaviruses, and new and emerging diseases such as Seneca A virus. These pathogens will be examined in the laboratory as well as in swine disease models to investigate mechanisms of pathogenesis, transmission, immunity, evolution and methods of intervention. Animal experiments to be conducted involve one of three general designs: 1) disease pathogenesis and transmission studies, 2) vaccine efficacy studies, 3) sow/neonatal studies. Knowledge obtained will be applied to break the cycle of transmission of these swine pathogens through development of better vaccines or other novel intervention strategies. A major research approach will be the use of reverse engineering and infectious clones to identify virulence components of each virus under study through mutational studies. Development of vaccines that provide better cross-protective immunity than what is currently available with today’s vaccines will be approached through vaccine vector platform development, attenuated strains for vaccines and other novel technologies. A key approach in the study of disease pathogenesis is to better understand the host response to viral infection to various viruses. This research on comparative host transcriptomics will provide insights on viral pathogenesis and possible virulence factors that will enable rational design of more effective vaccines and target possible novel intervention strategies.