# West Nile virus unmasked: from gene variability to future challenges

## TL;DR

This paper reviews the biology, spread, and control of West Nile virus, emphasizing its genetic variability and the need for improved surveillance and vaccines.

## Contribution

The paper integrates molecular, ecological, and clinical aspects of WNV to highlight future research and control priorities.

## Key findings

- WNV's genetic variability and quasispecies nature drive immune evasion and evolution.
- Climate change impacts vector distribution and global WNV spread.
- Integrated One Health surveillance and vaccine development are critical for outbreak mitigation.

## Abstract

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.

Overview of West Nile virus (WNV) biology, epidemiology, and control. The figure summarizes viral genome and proteins, replication cycle, intra-host variability, and epidemiological transmission. It also highlights clinical disease, prevention and control strategies, and current as well as experimental anti-WNV approaches.

Diagram illustrating the West Nile virus (WNV) replication cycle, including genome structure, replication process, epidemiological cycles, genetic variability, and anti-WNV strategies. Top left shows WNV genome and proteins, viral cycle, and replication steps. Right side highlights intra-host genetic variability with data visualization. Center depicts the epidemiological cycle involving birds, mosquitoes, and humans. Bottom sections detail current experimental control and prevention strategies,, including antibodies, RNA extraction, and detection methods. The West Nile Fever section outlines clinical aspects such as diagnosis and treatment.