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Title: North American domestic pigs are susceptible to experimental infection with Japanese encephalitis virus

Author
item PARK, SO LEE - Kansas State University
item HUANG, YAN-JANG S. - Kansas State University
item LYONS, AMY C. - Kansas State University
item AYERS, VICTORIA B. - Kansas State University
item HETTENBACH, SUSAN B. - Kansas State University
item McVey, David
item BURTON, KENNETH R. - Kansas State University
item HIGGS, STEPHEN - Kansas State University
item VANLANDINGHAM, DANA L. - Kansas State University

Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/19/2018
Publication Date: 6/19/2018
Citation: Park, S., Huang, Y., Lyons, A., Ayers, V., Hettenbach, S., McVey, D.S., Burton, K., Higgs, S., Vanlandingham, D. 2018. North American domestic pigs are susceptible to experimental infection with Japanese encephalitis virus. mBio. https://www.ncbi.nlm.nih.gov/pubmed/29742002.
DOI: https://doi.org/10.1038/s41598-018-26208-8

Interpretive Summary: JEV is currently the leading viral cause of fatal pediatric encephalitis in the Asia-Pacific region. Whilst its distribution is currently limited to parts of Asia, JEV can potentially expand and establish in new regions if competent mosquito vectors and susceptible amplifying vertebrate hosts, such as birds and pigs, are both present to support the enzootic transmission cycle. Alarmingly, previous studies have demonstrated that several North America mosquito and avian species are competent vectors and amplifiers of JEV. Here, we have determined that domestic pigs from North America are also susceptible to JEV infection. Using a local common commercial pig breed, we observed systemic infection, neuroinvasion, viral shedding, and virus persistence in challenged pigs. These findings have significant implications for the formulation of control strategies in the event of JEV introduction, as all three components of the transmission cycle, namely competent mosquitoes, amplifying birds, and swine are now known to be present in North America. In this study, the common North American white-line crossbreed of domestic pigs were challenged with a GI-b JEV strain to determine their susceptibility to the newly emerging genotype of JEV. Pathogenic outcomes and tissue tropism were characterized by detection of infectious viruses and viral genomes. Challenged animals developed detectable levels of viremia, systemic spread through lymphoid tissues, oronasal shedding, neuroinvasion, and viral persistence in the tonsils, suggesting that North American pigs are highly susceptible to JEV and are capable of sustaining its enzootic transmission cycle in the event of its introduction.

Technical Abstract: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is capable of causing severe and often fatal infections of the central nervous system in children. While significant disease is observed in humans, the transmission cycle is supported and maintained by viremic birds and pigs in endemic regions. Although JEV is regarded as a significant threat to the United States (U.S.), the susceptibility of domestic and feral swine to JEV infection has not been evaluated. In this study, commercial domestic pigs from North America were intravenously challenged with JEV to characterize infection and disease outcomes. Results showed that pigs were able to develop viremia and successfully seroconvert upon challenge. While most clinical signs were limited to those characteristic of nonspecific febrile illness, virus dissemination to various tissues and neuroinvasion was observed at the acute phase of infection. Furthermore, shedding of infectious virus was detected in nasal secretions, supporting the previous finding of an additional route of transmission. Quantification of viral RNA in tonsils supported previous findings of prolonged viral persistence. Based on this first report that domestic pigs in North America are susceptible to JEV infection, we believe that they could play an important potential role in a transmission cycle in the event of an introduction of JEV into the U.S. Shedding of virus in oral-nasal fluid could transmit the virus between pigs and also pose a risk to humans working with infected swine.