Japanese Encephalitis Virus and Other Closely Related Clinically Important Orthoflaviviruses—a Persistent Threat to Public and Animal Health

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 31 March 2026 | Viewed by 565

Special Issue Editor

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
Interests: swine virus; flavivirus; JEV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mosquito-borne viruses represent a dynamic and expanding threat to public and animal health, fueled by ecological disruption and globalization. Japanese encephalitis virus (JEV), a mosquito-borne orthoflavivirus, remains a significant global zoonotic pathogen which has profound implications for human and animal health. As the causative agent of Japanese encephalitis (JE), JEV induces severe neurological disease in humans and reproductive disorders in swine, its primary amplifying host.

In humans, JEV infection causes acute viral encephalitis with high mortality rates (20–30%) and frequent neurological complications, affecting 30–50% of survivors. The virus breaches the blood–brain barrier (BBB) through mechanisms involving receptor-mediated transcytosis, subsequently infiltrating the central nervous system (CNS). This invasion triggers neuroinflammatory cascades characterized by microglial activation, cytokine storms, and neuronal apoptosis, ultimately leading to fatal outcomes. Porcine infections manifest as reproductive failure clusters featuring stillbirths, mummified fetuses, and neonatal mortality, causing annual economic losses exceeding USD 500 million in endemic regions. Swine serve as critical amplification hosts due to sustained viremia and persistent tonsillar infection, maintaining viral transmission within mosquito–swine–human enzootic cycles.

Mosquito-borne viruses have imposed a huge burden on public health. JEV endemicity spans tropical and subtropical Asia-Pacific regions, exposing approximately 3 billion people to infection risk according to WHO estimates (World Health Organization, 2016. Japanese encephalitis vaccines: WHO position paper. Weekly Epidemiological Record 91, 69–88). Surveillance data from 2018–2022 indicate a 12% annual increase in human cases, attributed to vaccine accessibility gaps, the thermal instability of conventional vaccines, and climate-mediated expansion of Culex vector habitats. Domestic pig populations in rural ecosystems function as epidemiological sentinels, amplifying JEV transmission through mosquito vectors. Climate modeling predicts a 17-23% northward expansion of JEV transmission zones by 2040, threatening previously unaffected temperate regions.

This Research Topic seeks to advance JEV control strategies through multidisciplinary investigations of viral pathogenesis and transmission dynamics. We encourage submissions addressing, but not limited to, the following areas:

  1. Molecular mechanisms of JEV adaptation through experimental evolution studies;
  2. Genomic surveillance of natural JEV isolates from arthropod vectors and vertebrate hosts;
  3. Host–pathogen interactions governing JEV entry and systemic spread;
  4. Ecological determinants of JEV transmission in vector–host systems;
  5. Computational modeling of JEV infection networks and outbreak prediction;
  6. Next-generation vaccine platforms and broad-spectrum antiviral development.

Dr. Ke Liu
Guest Editor

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Keywords

  • Japanese encephalitis virus
  • mosquito-borne
  • orthoflaviviruses
  • public and animal health
  • transmission
  • infection
  • host

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Published Papers (1 paper)

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Research

18 pages, 1350 KB  
Article
mRNA Vaccine Against Japanese Encephalitis Virus Genotype IV Protects Against Lethal Infection
by Abigail L. Cox, Wilson Nguyen, Lucy Wales-Earl, Bing Tang, Kexin Yan, Jonathan Peters, Alexander A. Khromykh, Romain Tropée, Nigel A. J. McMillan, Andreas Suhrbier and Daniel J. Rawle
Viruses 2026, 18(2), 171; https://doi.org/10.3390/v18020171 - 28 Jan 2026
Viewed by 304
Abstract
In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested [...] Read more.
In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested two JEV GIV mRNA vaccines encoding prME, which provided protection against a lethal JEV GIV challenge in an Ifnar-/- mouse model. The vaccines were not codon optimized and included either the Native (full-length) or a Shorter signal peptide, with the latter missing the N-terminal n-region. Two vaccinations with 5 µg of the Shorter vaccine provided neutralizing antibody responses that were significantly lower but overlapped with those seen after vaccination with Imojev, a live attenuated vaccine approved for use in humans. Both mRNA vaccines provided approximately a five to six log reduction in viremia, ≥80% protection against overt disease and weight loss, and mortality. The paper illustrates in-country mRNA vaccine generation in response to a local outbreak, with JEV mRNA vaccines potentially emerging to be easier to manufacture, cheaper, and more suitable for immunocompromised individuals. Full article
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