West Nile Virus Infection

Abstract

West Nile virus (WNV) is an arthropod‐borne virus transmitted mainly by mosquito bites. Wild avifauna constitutes its natural reservoir. Mammals are dead‐end hosts as they generally do not develop a viraemia high enough to trigger a new infection cycle. WNV belongs to the Flavivirus genus and can be responsible for a disease known as WN fever. Humans and horses are the most sensitive hosts as they may develop severe neurological signs. WNV has a worldwide distribution and caused numerous outbreaks since the late 1990s, most notably in North America and Europe. Lineage 1 strains have caused the most severe outbreaks to date. However, the situation has recently evolved with the emergence in the late 2000s of pathogenic lineage 2 strains in South Africa, Russia and Eastern and Southern Europe. Many developments in the fields of WN diagnosis and vaccination have been described in the recent years and may help control WNV spread.

Key Concepts

  • West Nile virus (WNV) is a zoonotic arbovirus mainly transmitted by mosquitoes. It is an enveloped, positive‐stranded RNA virus belonging to the genus Flavivirus in the family Flaviviridae.
  • WNV has a wide geographical range that includes Europe, the Middle East, Western Asia, Africa, Australia (Kunjin virus) and North, Central and South America.
  • Most WNV infections are asymptomatic, but can be responsible for a disease known as WN fever (10–20% of WNV infections) or severe neurological signs (1–10% of WNV infections) in humans and horses.
  • Humans and horses are the most sensitive hosts.
  • Since the late 1990s, pathogenic WNV strains have begun to emerge.
  • Diagnosis can be difficult as flaviviruses are antigenically related.
  • There are no effective drugs or treatments against WNV infections.
  • Approved vaccines are available in equids, and human vaccines are under development.
  • Control of WNV outbreaks largely depends on vector control measures and interventions.

Keywords: West Nile; Flavivirus; arthropod‐borne virus infection; RNA virus; neuroinvasive; emergence; human; horse; bird

Figure 1. WNV transmission cycle. WNV is an arbovirus transmitted by mosquitoes, mainly from the genus Culex, and their reservoirs are wild birds. Transovarial transmission in Culex mosquitoes has been infrequently reported and could explain WNV overwintering in certain endemic areas (USA, Italy, etc.). Direct transmission via the oral route or direct contacts between birds can participate in WNV amplification, albeit generally at a low level. When virus circulation between reservoir birds and vectors is intense, humans and horses can get incidentally infected by bridge vectors (e.g. mosquitoes feeding both on birds and mammals). Humans and horses are dead‐end hosts for WNV as they do not develop viraemia high and long enough to infect naive mosquitoes. Human‐to‐human transmission can be observed through blood transfusion, organ transplantation and breast feeding upon recent infection of donors or mothers respectively.
Figure 2. Worldwide distribution of WNV, established with data collected on the pro‐Med website up to September 2014. Countries are coloured when WNV or WN fever/encephalitis has been detected in humans, birds, horses and other animals or vectors.
Figure 3. (a) Schematic representation of WNV viral particles, courtesy of ViralZone, SIB Swiss Institute of Bioinformatics. Left, representation of envelope (E) and membrane proteins at the surface of the virion. Capsid proteins form a shell protecting the viral RNA. Right, organisation of surface E dimers. Reproduced with permission from ViralZone, SIB Swiss Institute of Bioinformatics. (b) Schematic representation of WNV genomic organisation and viral proteins. Genomic RNA is capped at its 5′ end and non‐polyadenylated at its 3′ end. WNV RNA encodes for a polyprotein of 3300 amino acids, subsequently cleaved into 10 viral proteins: three structural proteins (C, prM and E) and seven non‐structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). Structural proteins are involved in viral assembly, host tropism, binding and fusion to host cell. Non‐structural proteins play key roles in RNA replication, control of host immune reactions and viral morphogenesis. Cleavages at the C–prM, prM–E, E–NS1, NS4A–NS4B and probably also the NS1–NS2A junctions are performed by the host signal peptidase located within the lumen of the ER. The remaining cleavage bonds are processed by the viral NS3 protease. RdRp, RNA‐dependent RNA polymerase. (c) Schematic representation of WNV replication cycle. WNV interacts with its host target cell through the envelope protein that contains the receptor binding domain. The viral particle is then endocytosed. Acidic pH of the endosome induces conformation changes in the envelope protein, leading to the exposure of its fusion peptide. The viral capsid is then freed from the endosome, a step followed by decapsidation of the genomic RNA. The positive‐sense RNA is immediately translated and synthesised NS viral proteins form a replication complex at endoplasmic reticulum membranes. Newly synthesised genomic RNAs are encapsidated, bud into the ER lumen and are transported in fusion vesicles. New virions are released through the exocytic pathway. ER, endoplasmic reticulum; pi, post infection.
Figure 4. (a) Cartography of WNV infection sites and pathology in humans and birds. Note: Pathology displayed for birds depends on bird species and/or WNV lineage (Gamino and Höfle, ). (b) Kinetics of infection markers after WNV inoculation into the skin. Primary viraemia can be detected 3–4 days post infection in mammals. Shortly afterwards, WNV is detected in the urine of patients. IgM antibodies are detectable in the blood and the cerebrospinal fluid approximately 4–7 days after infection with a peak 2–8 days after the onset of neurological symptoms and can last from 3–4 months to up to 1 year. IgG immunoglobulins are produced in the blood from day 5–12 post infection and can persist for several years in the blood.
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Bahuon, Céline, Lecollinet, Sylvie, and Beck, Cécile(May 2015) West Nile Virus Infection. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023274]