Because of their dependence on specific vectors and different natural hosts, flaviviruses have distinct geographical distributions. YFV is endemic in tropical and subtropical regions in Africa and South-America and causes an estimated

200,000 cases with 30,000 deaths annually [3]. Geographically, the endemic regions of DENV overlap with those of YFV in Africa and South-America. However, DEN extends not only to Middle America and southern parts of North America but also to 17-AAG supplier large parts of South-East Asia, where YFV is not found [4]. Infections with DENV are usually mild but extremely frequent, with about 100–200 million infections every year [5] and [6]. In a small proportion of patients, the disease can exacerbate and lead to dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). Annually, about 500,000 such cases with more than 20,000 deaths are recorded [7]. The endemic areas of JEV overlap with those of DENV in South-East Asia, but JEV is transmitted by different mosquitoes and has different natural hosts [8] and [9]. JEV causes severe encephalitis and 25–30% of the 50,000 cases occurring every year

are fatal [9]. Gefitinib research buy In contrast to these mosquito-borne viruses, TBEV is not found in the tropics/subtropics but in many parts of Europe as well as Central and Eastern Asia [10]. In these areas, it accounts for one of the most important CNS infections in adults with more than 10,000 cases per year [11]. WNV is an example of the potential of flaviviruses to emerge suddenly in previously unaffected geographical areas. It was known to be endemic in parts of Africa, Europe, Asia, and Australia – causing sporadic cases or small outbreaks of CNS disease – before it first appeared at the East coast of the USA in 1999 and rapidly spread over the North-American continent, to Central-America and finally to South-America [12].

In the peak year of 2003, 9862 human cases and 264 deaths due to WNV infections were documented in the US [13] and in the light of continued expansion, the need for an effective vaccine appeared to gain high priority [14]. Since then, the annual numbers of cases in the US have declined significantly [15], with a parallel decrease in the interest mafosfamide for commercial vaccine development. Like all members of the Flaviviridae family, flaviruses are small enveloped positive stranded RNA viruses. Mature viruses have a diameter of 50 nm and contain only three structural proteins, designated C (capsid), E (envelope) and M (membrane) ( Fig. 1). Particle assembly takes place in the endoplasmic reticulum and first leads to the formation of immature viruses that contain the precursor of M (prM) ( Fig. 1 and Fig. 2) [16] which is proteolytically cleaved in the trans-Golgi network during exocytosis by a cellular protease before the virions are released from infected cells ( Fig. 2) [17], [18] and [19].