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

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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