West Nile virus (WNV) is an enveloped, positive-sense single-stranded RNA virus in the genus Flavivirus. It is transmitted primarily by Culex mosquitoes in a bird‑mosquito cycle and causes West Nile fever and neuroinvasive disease in humans and horses.
Genome and Virology
The WNV genome is an approximately 11-kilobase positive-sense RNA molecule encoding a single open reading frame. Translation produces a polyprotein that is co- and post-translationally cleaved into three structural proteins (capsid, premembrane/membrane and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). The envelope glycoprotein mediates attachment to host receptors such as DC‑SIGN and integrins; viral entry occurs via clathrin-mediated endocytosis, with low endosomal pH triggering fusion. Replication takes place on modified endoplasmic reticulum membranes. NS3 acts as a serine protease and helicase, while NS5 functions as an RNA-dependent RNA polymerase and methyltransferase producing negative-strand intermediates and new genomes. Virions assemble and bud into the endoplasmic reticulum, mature in the trans‑Golgi network and exit via exocytosis. WNV infects a broad range of vertebrate cells, including avian endothelial cells, dendritic cells, monocytes and neurons; lineage 1 and lineage 2 are the major genetic groups, differing in geographic distribution and pathogenicity.
Epidemiology and Disease Impact
First isolated from a febrile patient in Uganda in 1937, WNV is now endemic in Africa, Europe, the Middle East, Asia and the Americas. The virus emerged in the Western Hemisphere in 1999, causing an outbreak in New York City that spread across North America within a few years. Birds serve as the primary amplifying hosts, while humans and horses are incidental dead-end hosts because they develop low-level viremia insufficient for mosquito transmission. Most human infections are asymptomatic; around 20 % develop an illness characterised by fever, headache, myalgia, arthralgia and rash. Less than 1 % of infections lead to neuroinvasive disease, manifesting as meningitis, encephalitis or acute flaccid paralysis, with higher risk in older or immunocompromised individuals. Transmission occurs mainly through mosquito bites; rare routes include blood transfusion, organ transplantation and transplacental transmission. There is no licensed human vaccine or specific antiviral treatment; supportive care is the main therapy. Prevention focuses on mosquito control, use of repellents, window screens and removal of standing water, as well as surveillance of bird and mosquito populations. An inactivated vaccine is available for horses. West Nile virus has become a significant cause of arboviral encephalitis worldwide. Understanding its virology, transmission cycle and risk factors for severe disease guides public health surveillance and vector control programs. Related Terms: Zika Virus, Dengue Virus, Yellow Fever Virus, Japanese Encephalitis Virus, Culex mosquitoes