Phylogenetic analysis demonstrates that flaviviruses cluster not just antigenically but also group according to their known transmission vectors. The antigenic relationships among flaviviruses. The genetic differences amongst flaviviruses result in both conserved and species-specific attributes, such as cellular and tissue tropism upon infection and, importantly for the purposes of this review, antigenic properties. Phylogenetic analysis has shown that flaviviruses cluster in genomic similarity according to their dominant vector ( Figure 1), which also is a major contributing factor to the often-overlapping global distribution patterns of each flavivirus. Additional flaviviruses have no known vector ( 2) while others are thought to be restricted to insects or bats and are not reported to cause human disease ( 3). Yet other flaviviruses that are human pathogens, such as Kyasanur forest disease (hemorrhagic) and Powassan (encephalitic) viruses, are tick-borne. Some of the most prominent mosquito-borne flaviviral human pathogens include the hemorrhagic fever viruses, dengue (DENV) and yellow fever (YFV), and neurotropic viruses, such as West Nile (WNV), Japanese encephalitis (JEV), Saint Louis encephalitis (SLEV), and Zika (ZIKV). The viral genome encodes for three structural and seven non-structural proteins that are needed for virus replication and assembly ( 1). Flaviviruses are enveloped single-stranded positive-sense RNA viruses that share conserved structural and genomic features ( 1).
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