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Research Project: Japanese Encephalitis Virus Prevention and Mitigation Strategies

Location: Foreign Arthropod Borne Animal Disease Research

2018 Annual Report

Identify factors associated with Flavivirus infections, pathogenesis, and maintenance in vectors and animal hosts to inform prevention and mitigation strategies including identifying factors associated with JEV maintenance in relevant mosquito vectors; characterizing susceptibility, pathogenesis, and clinical disease of JEV in domestic pigs; and characterizing vector-host interactions with JEV transmission. Subobjective 1A: Identify factors associated with JEV maintenance in relevant mosquito vectors. Subobjective 1B: Characterize susceptibility, pathogenesis, and clinical disease of JEV in domestic pigs. Subobjective 1C: Characterize vector-host interactions associated with JEV transmission.

Japanese encephalitis virus (JEV) is an arthropod-borne virus (arbovirus) endemic to Asia, where it is the most important cause of viral encephalitis in humans and a significant cause of reproductive and neonatal loss in swine. JEV transmission does not currently occur in the U.S.; however, North American mosquitoes have recently been demonstrated to be competent virus vectors. JEV is closely related to the West Nile Virus, a formerly foreign arbovirus that was introduced into the U.S. in 1999 and quickly became established across most of the country. Pigs are considered to be primary amplifying hosts for JEV; infected pigs are capable of replicating the virus to high titers and are thought to fuel outbreaks by serving as sources of virus for mosquitoes. Although JEV has been studied for 7 decades, considerable knowledge gaps exist regarding its transmission, particularly in the pig-mosquito segment of its cycle. The goal of this project is to better understand mammalian host (pig) and vector (mosquito) factors that permit transmission of JEV in order to identify actions to break the transmission cycle and develop new detection and prevention tools. These gains will support not only livestock health and food security, but also the protection of human health.

Progress Report
This report documents the progress of the newly established project, 3020-32000-014-00D, entitled “Japanese Encephalitis Virus Prevention and Mitigation Strategies,” which started in late June of 2018. This project was preceded by a bridging project, 3020-32000-011-00D, entitled “Predictive Biology of Emerging Vector-Borne Viral Diseases.” For information on that project, please see the final report for 3020-32000-011-00D. In the short time this project has been active, we have made progress in all three of its subobjectives, which address Component 1 (Biodefense) of the 2016-2021 Animal Health National Program (NP 103) Action Plan. This project constitutes a new program for the Agency and is thus in a phase of intensive protocol and reagent development following the approval of its research plan by ARS’s Office of Scientific Quality Review. Under all three subobjectives, we have designed protocols, produced new detailed Standard Operating Procedures (SOPs), and completed the federal and local regulatory approval processes required to begin work on the new project. Under Subobjectives B and C, we have developed new assay systems to measure the impact of viral infections on porcine immune cells. Using a cell line developed by an ARS scientist in Clay Center, Nebraska, we have applied molecular and cellular assays to generate a new profile of macrophage responses to arthropod-borne viral infections.

1. Assay system developed for the study of arboviral infections in porcine immune cells. ARS scientist in Manhattan, Kansas developed a framework to study the cellular mechanisms by which arthropod-borne viral infections kill porcine immune cells by applying a combination of assays typically used in cancer studies. We combined this with measurements of immune system gene expression to better characterize virus impacts and mechanisms in the immune systems of infected pigs. This assay system will enable us to better understand the mechanisms by which Japanese encephalitis virus infects, and causes disease in, swine. In addition, it has already proven useful in our study of other viruses, specifically Rift Valley fever. Understanding the mechanisms of disease pathogenesis is fundamental to developing, and planning for, countermeasures. This information may be useful to partner agencies and other ARS customers for the development of response strategies.

Review Publications
Lyons, A., Huang, Y., Park, S., Ayers, V., Hettenbach, S., Higgs, S., Mcvey, D.S., Noronha, L.E., Hsu, W., Vanlandingham, D. 2018. Shedding of Japanese encephalitis virus in oral fluid of infected swine. Vector-Borne and Zoonotic Diseases. 10.1089/vbz.2018.2283.
Oliverira, A., Etcheverry Hernandez, L., Strathe, E., McVey, D.S., Piaggio, J., Cohnstaedt, L.W., Cernicchiaro, N. 2018. Quantification of vector and host competence for Japanese encephalitis virus: a systematic review of the literature. Preventive Veterinary Medicine.