1. 8. Dengue VirusThe causative agent of dengue is dengue virus (DENV), a group of four closely related but antigenically distinct flaviviruses. They are assumed to have evolved independently from ancestral sylvatic viruses 100 to 1,500 years ago (Wang et al., 2000). The four groups are known as serotypes and referred to as dengue virus type 1 (DENV-1), dengue virus type 2 (DENV-2), dengue virus type 3 (DENV-3). ) and dengue virus type 4 (DENV-4). 1. 8. 1. TaxonomyThere are three genera in the family Flaviviridae (formerly known as Group B arboviruses), namely Flaviviruses, Pestiviruses and Hepaciviruses. The dengue virus is part of the Flavivirus genus which includes 55 identified virus species (ICTVdB, 2006). The word Flavi is a derivative of the Latin "flavus" meaning "yellow" and the type species of the genus is a yellow fever virus (YFV). Flaviviruses are so named because of the jaundice seen in patients with yellow fever. Many flaviviruses are important human pathogens, including dengue viruses, yellow fever virus, Japanese encephalitis virus (JEV), West Nile virus (WNV), and encephalitis virus. tick-borne (TBEV). Flaviviruses are primarily transmitted by mosquitoes and ticks, while some have no known vector. Dengue was one of the groups classified when early researchers serologically divided the flaviviruses into eight antigenic complexes using cross-neutralization assays. However, many viruses, for example the prototype genus YFV, could not be affiliated with any complex (Calisher et al., 1989). When sequence data became available, phylogenetic inference from molecular data showed agreement with antigen complex classification. Additionally, it revealed the ...... middle of paper ...... its viral fitness. Most mutations in DENV genomes are deleterious, which plays an important role in the evolution of DENV. Another major factor for DENV adaptation is diversification related to transmission in various geographic regions. Four serotypes of dengue virus can co-circulate in endemic areas because immunity against one serotype does not protect against infection with a heterologous serotype. This is likely the result of selection driven by the restrictive effects of cross-protective antibodies produced against heterologous serotypes. Strains of dengue virus, capable of escaping this neutralization process, have a significant competitive advantage and become the dominant lineages. This evolutionary adaptation has not only allowed the co-circulation of the 4 serotypes, but also has a great influence on their pathogenicity for humans...