Changing patterns of West Nile virus transmission: altered vector competence and host susceptibility

Abstract

West Nile virus (WNV) is a flavivirus (Flaviviridae) transmitted between Culex spp. mosquitoes and avian hosts. The virus has dramatically expanded its geographic range in the past ten years. Increases in global commerce, climate change, ecological factors and the emergence of novel viral genotypes likely play significant roles in the emergence of this virus; however, the exact mechanism and relative importance of each is uncertain. Previously WNV was primarily associated with febrile illness of children in endemic areas, but it was identified as a cause of neurological disease in humans in 1994. This modulation in disease presentation could be the result of the emergence of a more virulent genotype as well as the progression of the virus into areas in which the age structure of immunologically naïve individuals makes them more susceptible to severe neurological disease. Since its introduction to North America in 1999, a novel WNV genotype has been identified that has been demonstrated to disseminate more rapidly and with greater efficiency at elevated temperatures than the originally introduced strain, indicating the potential importance of temperature as a selective criteria for the emergence of WNV genotypes with increased vectorial capacity. Even prior to the North American introduction, a mutation associated with increased replication in avian hosts, identified to be under adaptive evolutionary pressure, has been identified, indicating that adaptation for increased replication within vertebrate hosts could play a role in increased transmission efficiency. Although stable in its evolutionary structure, WNV has demonstrated the capacity for rapidly adapting to both vertebrate hosts and invertebrate vectors and will likely continue to exploit novel ecological niches as it adapts to novel transmission foci.

Figure 1.

Genomic organization of the WNV genome. Three structural proteins (C, prM, E) and seven nonstructural proteins (NS1, 2A, 2B, 3, 4A, 4B and 5) are translated as a single polyprotein directly from the 11 Kb positive-sense RNA genome.

Figure 2.

Transmission cycles of WNV. Transmission occurs between ornithophilic mosquito species (Culex spp.) and passeriform avian hosts. Birds typically manifest high viremias capable of exceeding oral infection thresholds for many mosquito vectors. Humans and equines fail to generate sufficient viremia for the infection of mosquito hosts and are deemed “dead end” or tangential hosts. Red: Avian mortality was first identified in a migratory stork and subsequently in commercially farmed geese in the late 1990s and has subsequently been associated with widespread mortality among numerous North American avian species (in particular, corvids). (A color version of this figure is available at www.vetres.org.)

Figure 3.

Maximum likelihood phylogenetic tree of 21 complete genomes of WNV. Viruses are grouped according to four described lineages of WNV (excluding the lineage 5 Indian group) and the genetic residue at each NS3-249 site is indicated. The three independent emergences of the NS3-249P genotype has been denoted on the tree. In each case an NS3-249Pro genotype emerged (designated in bold black) from a predecessor genotype (Thr; designated in grey). The asterisks represent nodes with bootstrap support values > 95%.