The virus

WNV is classified as a member of the genus Flavivirus in the Flaviviridae family, which contains more than 70 viruses, with approximately 40 of them being human pathogens (e.g. Dengue fever viruses, tick-borne encephalitis virus, Japanese encephalitis virus, Yellow fever virus, etc.). On the basis of serological cross-reactivity, Flavivirus genus is subdivided into 12 antigenic serocompexes, and WNV belongs to the Japanese encephalitis serocomplex. Although WNV strains cluster into various genetic lineages, most of the reported pathogenic strains belong to two major lineages, 1 and 2**.  Lineage 1 is distributed almost worldwide, while lineage 2 was initially thought to be restricted to sub-Saharan Africa and Madagascar. However, since 2004, lineage 2 strains caused large outbreaks in humans in several European countries. Lineage 3 consists of Rabensburg virus, isolated from Culex pipiens in 1997 in the Czech Republic, near the Austrian border. Lineage 4 comprises isolates from Caucasus region in Russia, first detected in 1988 from a Dermacentor tick, and later isolated from mosquitoes. Lineage 5 (or clade 1c) contains isolates from India obtained from humans and mosquitoes. A putative lineage 6 consists of a sequence detected in 2006 in Culex pipiens mosquitoes in southern Spain, while Koutango virus isolated in Senegal might represent a seventh lineage, although it is currently categorized as a separate species.  **Since all outbreaks in Europe, Israel and America were caused by WNV lineage 1 strains, it was suggested that this is the pathogenic lineage, while WNV lineage 2 was considered as not pathogenic. However, recent studies in Africa showed that there are pathogenic strains belonging to this lineage. In general, it seems that the role of WNV lineage 2 has been previously underestimated and that the virulence is associated with the specific strain rather than the lineage, the location or the year of isolation