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.