REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1690827
West Nile Virus Unmasked: from Gene Variability to Future Challenges
Provisionally accepted
Samuel Prieto-Vega1
Alfredo Berzal-Herranz2
Juan J Garrido3
Armando Arias4
Ana Grande-Pérez5
Ana María Fernández-Escamilla6*
Maria Montoya7*- 1Universidad de Malaga Facultad de Ciencias, Málaga, Spain
- 2Instituto de Parasitologia y Biomedicina Lopez-Neyra, Granada, Spain
- 3Universidad de Cordoba, Córdoba, Spain
- 4Universidad de Castilla-La Mancha - Campus de Albacete, Albacete, Spain
- 5Universidad de Malaga, Málaga, Spain
- 6Universidad Miguel Hernandez de Elche Instituto de Investigacion Desarrollo e Innovacion en Biotecnologia Sanitaria de Elche, Alicante, Spain
- 7Spanish National Research Council (CSIC), Madrid, Spain
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West Nile virus (WNV) is a mosquito-borne orthoflavivirus with a complex transmission cycle involving avian reservoirs and mosquito vectors. Although no precise global infection figure exists, conservative estimates based on seroprevalence data suggest between 4 and 16 million infections annually. With an approximate mortality rate of 6–7% among reported cases, WNV poses a significant public health concern across continents. This review provides a comprehensive overview of WNV molecular biology, including genome organization, protein maturation, replication mechanisms, the functional roles of untranslated regions (UTRs) and post-translational modifications in viral adaptation. Particular attention is given to intrahost genetic variability and the quasispecies nature of WNV as key drivers of immune evasion and viral evolution. The ecological and epidemiological dynamics of WNV are also discussed in the context of climate change and its impact on vector distribution and global viral spread. Additionally, the review details clinical manifestations, pathogenesis, diagnostic tools, and current therapeutic strategies. Emerging approaches for prevention and control are explored, including entomological surveillance, vaccine development, and novel antiviral candidates such as targeted peptides, antibodies and lethal mutagenesis. Given the pressing challenges associated with WNV, this review underscores the importance of integrated One Health surveillance systems and accelerated vaccine development to mitigate future outbreaks, highlighting the intersection of virology, immunology, ecology, and global health.
Keywords: West Nile virus, genetic variability, Therapeutics, host-virus interaction, West Nile Fever
Received: 22 Aug 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Prieto-Vega, Berzal-Herranz, Garrido, Arias, Grande-Pérez, Fernández-Escamilla and Montoya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ana María Fernández-Escamilla, ana.fernandeze@umh.es
Maria Montoya, maria.montoya@cib.csic.es
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.