Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography

Phylogenetic analysis of the Flavivirus genus, using either partial sequenc es of the non-structural 5 gene or the structural envelope gene, revealed a n extensive series of clades defined by their epidemiology and disease asso ciations. These phylogenies identified mosquito-borne, tick-borne and no-kn own-vector (NKV) virus clades, which could be further subdivided into clade s defined by their principal vertebrate host. The mosquito-borne flavivirus es revealed two distinct epidemiological groups: (i) the neurotropic viruse s, often associated with encephalitic disease in humans or livestock, corre lated with the Culex species vector and bird reservoirs and (ii) the non-ne urotropic viruses, associated with haemorrhagic disease in humans, correlat ed with the Aedes species vector and primate hosts. Thus, the tree topology describing the virus-host association may reflect differences in the feedi ng behaviour between Aedes and Culex mosquitoes. The tick-borne viruses als o formed two distinct groups: one group associated with seabirds and the ot her, the tick-borne encephalitis complex viruses, associated primarily with rodents. The NKV flaviviruses formed three distinct groups: one group, whi ch was closely related to the mosquito-borne viruses, associated with bats; a second group, which was more genetically distant, also associated with b ats; and a third group associated with rodents. Each epidemiological group within the phylogenies revealed distinct geographical clusters in either th e Old World or the New World, which for mosquito-borne viruses may reflect an Old World origin. The correlation between epidemiology, disease correlat ion and biogeography begins to define the complex evolutionary relationship s between the virus, vector, vertebrate host and ecological niche.