West Nile virus (WNV) is one of the most evident examples of emerging/re-emerging pathogens one can nominate, which is characterized by occasional virulent epizootic outbreaks. Despite intensive research done since its first appearance in the Americas in 1999, many aspects of its molecular biology, epidemiology, ecology, pathogenesis and life cycle are still poorly understood. Being a generalist pathogen par excellence, its eco-epidemiology is extraordinarily complex, involving hundreds of different vectors and hosts, which differ between locations. In addition, as other RNA viruses lacking proofreading replication, its genome is highly variable and consequently of extraordinary plasticity. As a result, many WNV variants have evolved independently in different parts of the world. As the virus moves from one area to another, either by nature, through migrating birds, or by human influence (commerce and/or other activities), different WNV variants (lineages) from different origins can coexist and co-evolve in a particular area. This is the case in Europe, with at least five of seven WNV lineages identified to date. This situation is clearly different from that of North America. However, most studies on WNV currently come from the USA, biasing the knowledge available not only toward the virus there -a serious bias with important consequences influencing, for instance, diagnostic methods- but also to the WNV ecology in hosts and vectors.In the present Project we propose to conduct comprehensive studies on the WNV situation in Europe and affected surrounding countries that accounting for the peculiarities of WNV eco-epidemiology in this region. Moreover we will strive to cover knowledge gaps regarding its ecology, epidemiology and pathogenesis in Europe. Finally, the Project aims to develop new tools and strategies for research on treatment and prevention of WNV disease, as well as to produce new diagnostic methods, taking Euro-Mediterranean peculiarities into account