Japanese encephalitis virus and infection of feral phenotype swine

Authors: PARK, SO LEE - Kansas State University; HUANG, YAN-JANG - Kansas State University; LYONS, AMY - Kansas State University; AYERS, VICTORIA - Kansas State University; HETTENBACH, SUSAN - Kansas State University; MCVEY, D. - Kansas State University; Noronha, Leela; BURTON, KENNETH - Kansas State University; HIGGS, STEPHEN - Kansas State University; VANLANDINGHAM, DANA - Kansas State University

Submitted to: Vector-Borne and Zoonotic Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2023
Publication Date: 11/28/2023
Citation: Park, S., Huang, Y.S., Lyons, A.C., Ayers, V.B., Hettenbach, S.M., Mcvey, D.S., Noronha, L.E., Burton, K.R., Higgs, S., Vanlandingham, D.L. 2023. Japanese encephalitis virus and infection of feral phenotype swine. Vector-Borne and Zoonotic Diseases. 25(12):605-669. https://doi.org/10.1089/vbz.2023.0030.
DOI: https://doi.org/10.1089/vbz.2023.0030

Interpretive Summary: Japanese encephalitis virus (JEV) is a mosquito-transmitted virus endemic to the Asia-Pacific region. Outbreaks of JEV are often associated with agricultural activities in endemic areas because domestic swine can develop a viremia that provides a source of infection for competent mosquitoes. Modern domestic pigs originated from the domestication of feral pigs or wild boars. Samples from wild boars in Korea and Japan show that feral pigs in the Asia Pacific region can be exposed to JEV in nature; however, it is not known whether infected feral pigs can produce enough virus to support the transmission cycle of JEV. In this study, the Sinclair miniature research pig was used as a representative model of feral pigs. Pigs that were challenged with a wildtype strain of JEV developed viremia, oronasal shedding, systemic spread, and neurotropic disease. Taken together, these findings are the first direct evidence to show that feral-domestic pig hybrids can potentially support the transmission cycle of JEV in nature.

Technical Abstract: Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves Culex spp. mosquitoes and Ardeid birds, with domestic pigs (Sus scrofa domestica) being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population. Although many studies have concluded that domestic pigs play an important role in the transmission cycle of JEV, and infection of humans, the role of feral pigs in the transmission of JEV remains unclear. Since domestic and feral pigs are the same species, and because feral pig populations in the U.S. are increasing and expanding geographically, the current study aimed to test the hypothesis that if JEV were introduced into the U.S., that feral pigs might play a role in the transmission cycle. Since studies using feral swine were not possible, our approach was to use Sinclair miniature pigs, derived from crossing miniature domestic pig with four strains of feral pigs. These Sinclair pigs exhibit the feral phenotype and when intradermally inoculated with genotype 1b JEV, became viremic and displayed pathological outcomes similar to those observed in domestic swine. Based on these findings, we conclude that in the event of JEV being introduced into the U.S., feral pig populations could contribute to establishment and maintenance of a transmission cycle of JEV, that could lead to the virus becoming endemic in the U.S.