Project Number: 3022-32000-025-000-D
Project Type: In-House Appropriated
Start Date: Jan 20, 2022
End Date: Jan 19, 2027
OBJECTIVE 1: Identify factors associated with Flavivirus infections, pathogenesis, and maintenance in vectors and animal hosts to inform prevention and mitigation strategies. • Identify factors associated with JEV maintenance in relevant insect vectors. • Characterize susceptibility, pathogenesis, and clinical disease of JEV in swine. • Characterize vector-virus-host interactions associated with JEV transmission. Sub-objective 1.A. Evaluate the ability of an emerging JEV genotype to infect and replicate in North American domestic swine and mosquito vectors. Sub-objective 1.B. Investigate potential roles of North American feral swine and biting midges in JEV transmission. OBJECTIVE 2: Identify and develop JEV control measures in swine. • Develop detection measures fit for JEV surveillance in swine. • Develop JEV vaccines for swine that will prevent virus amplification. • Develop control measures to protect swine from JEV-infected Culex mosquitoes. Sub-objective 2.A. Qualification of point-of-need diagnostics for Japanese encephalitis virus infections. Sub-Objective 2.B. Develop and evaluate novel vaccine platforms to prevent JEV transmission from swine. Sub-Objective 2.C. Develop control measures to protect swine from JEV-infected Culex mosquitoes.
Japanese encephalitis virus (JEV) is a zoonotic arthropod-borne pathogen native to Asia and the Pacific Rim, where it is a significant cause of reproductive and neonatal loss in swine and severe encephalitis and death in humans. JEV is transmitted to vertebrate hosts by infected mosquito vectors and has demonstrated an ability to emerge in new geographic regions that contain competent vectors and susceptible hosts. JEV does not currently circulate in the United States (U.S.); however, the risk of its introduction has been assessed as high (Oliveira et al. 2020). Significant research gaps exist regarding U.S. vulnerability following an introduction of JEV, including the range of native vectors and hosts capable of sustaining transmission and whether U.S. mosquitoes and livestock are vulnerable to emerging genotypes of JEV. This project will address these, and other gaps, by evaluating the ability of an emerging JEV genotype to infect and replicate in domestic swine and mosquitoes and by investigating the potential roles of previously uncharacterized wildlife hosts and insect vectors in JEV transmission. These studies will use in vitro and in vivo infection models to investigate the effects of wild-type JE viruses on insect vectors and mammalian hosts (Objective 1). Next generation sequencing and genomic analyses will be used to study vector-virus-host interactions to determine effects that hosts and vectors have on virus populations. Additionally, measures to protect swine from JEV will be developed including molecular diagnostic assays, novel vaccines, and a spatial insect repellent device (Objective 2). The knowledge gained will be used to inform risk assessments and predictive models and help identify target points to guide diagnostic development, surveillance programs, and control strategies. Together, these measures will help strengthen the U.S. disease prevention and response framework for rapidly stopping foreign animal disease incursions to protect the health and profitability of U.S. livestock.