Mosquito saliva modulates Japanese encephalitis virus infection in domestic pigs

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. SCOTT - University Of Nebraska; Noronha, Leela; BURTON, KENNETH - Kansas State University; HSU, WEI-WEN - Kansas State University; HIGGS, STEPHEN - Kansas State University; VANLANDINGHAM, DANA - Kansas State University

Submitted to: Frontiers in Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/13/2021
Publication Date: 9/17/2021
Citation: Park, S., Huang, Y.S., Lyons, A.C., Ayers, V.B., Hettenbach, S.M., McVey, D., Noronha, L.E., Burton, K.R., Hsu, W., Higgs, S., Vanlandingham, D.L. 2021. Mosquito saliva modulates Japanese encephalitis virus infection in domestic pigs. Frontiers in Virology. 1. Article 724016. https://doi.org/10.3389/fviro.2021.724016.
DOI: https://doi.org/10.3389/fviro.2021.724016

Interpretive Summary: Japanese encephalitis virus (JEV) is a flavivirus that is transmitted by mosquitoes and is endemic to the Asia-Pacific region. It is a leading cause of viral encephalitis in children in Asia as well as an agricultural pathogen that causes encephalitis in piglets and reproductive disease in adult pigs. Mosquito saliva has previously been shown to worsen symptoms of flavivirus infections in mouse models. The objective of this study was to determine whether components of mosquito saliva impact JEV infections in pigs. Salivary gland extract collected from Culex quinquefasciatus mosquitoes co-injected with JEV reduced fevers in domestic piglets and shortened the amount of time that virus was shed by the nasal route. The amount of virus that was found in the central nervous system and blood did not significantly change. These findings suggest that mosquito saliva may affect the outcomes of flavivirus infections differently in natural amplifying hosts like pigs, compared to animals that do not play a role in virus transmission. This information may help improve our understanding of how these types of viruses interact with animal hosts to cause disease.

Technical Abstract: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is the leading cause of pediatric viral encephalitis in Asia. JEV is transmitted by Culex species mosquitoes that also vector several zoonotic flaviviruses. Despite the knowledge that mosquito saliva contains molecules that may alter flavivirus pathogenesis, whether or not the deposition of viruses by infected mosquitoes has an impact on the kinetics and severity of JEV infection has not been thoroughly examined, especially in mammalian species involved in the enzootic transmission. Most JEV pathogenesis models were established using needle inoculation. Mouse models for West Nile and dengue viruses have shown that mosquito saliva can potentiate flavivirus infections and exacerbate disease symptoms. In this study, we determined the impact of mosquito salivary components on the pathogenesis of JEV in pigs, a species directly involved in its transmission cycle as an amplifying host. Interestingly, co-injection of JEV and salivary gland extract collected from Culex quinquefasciatus produced milder febrile illness and shortened duration of nasal shedding but had no demonstrable impact on viremia and neuroinvasion. Our findings highlight that mosquito salivary components can differentially modulate the outcomes of flavivirus infections in amplifying hosts and in mouse models.