Differential Virulence and Pathogenesis of West Nile Viruses

Abstract

West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%–40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS), and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.

Evaluation of Cross-Protection of a Lineage 1 West Nile Virus Inactivated Vaccine against Natural Infections from a Virulent Lineage 2 Strain in Horses, under Field Conditions

“…However, escape from neutralization has been associated with the L 312 A substitution, which was present in the Nea Santa-Greece-2010 strain, as it is in several WNV strains (60). No changes were observed in residues W 101 , G 106 , and L 107 , antigenic sites of the fusion loop located within DII (DII-FL) (residues 98 to 109), which act as targets of cross-NAbs among different species of the genus Flavivirus (61)(62)(63). Despite the L 312 A substitution, the findings of the present study ultimately suggest that under field conditions, adequate cross-neutralization is capable of providing a high degree of protection.…”

“…Different WNV lineages, characterized by varying levels of virulence and neuroinvasiveness, cocirculate in Europe (63), and knowledge regarding cross-protection is a prerequisite. However, since outbreaks in horses were limited and unpredictable, immunizations have been performed extensively (26), regardless of the degree of cross-protection between circulating and vaccine strains.…”

Current developments in understanding of West Nile virus central nervous system disease

“…Based on genetic analysis, at least eight lineages of WNV are now recognized; however, human pathogenic strains belong to lineages 1 and 2, with lineage 1a strains accounting for most recent epidemics associated with significant neuroinvasive disease [6]. Extensive studies of the molecular epidemiology of WNV strains have been conducted.…”

Putative novel lineage of West Nile virus in Uranotaenia unguiculata mosquito, Hungary

“…WNV-3 is represented by strain Rabensburg 97-103 isolated from Culex pipiens in Czech Republic, WNV-4 is represented by strain LEIVKrnd88-190 isolated from Dermacentor marginatus ticks in the Caucasus, whereas WNV-5 (strain 804994) was identified in India. Representative strains of other putative lineages include the strain KUN MP502-66 from Malaysia (WNV-6), Dak Ar D 5443 from Senegal (WNV-7) and HU2925/06 from Spain (WNV-8) [3]. In the past decade, WNV-2 has emerged in Europe and caused outbreaks in Hungary, Austria, Greece, Italy, Romania, Serbia and Croatia, and now has become endemic in many [1].…”