of asia. phylogenetic studies of the west nile virus has shown that it emerged as a distinct virus around 1000 years ago. this initial virus developed into two distinct lineages, lineage 1 and its multiple profiles is the source of the epidemic transmission in africa and throughout the world. lineage 2 was considered an africa zoonosis. however, in 2008, lineage 2, previously only seen in horses in sub-saharan africa and madagascar, began to appear in horses in europe, where the first known outbreak affected 18 animals in hungary in 2008. lineage 1 west nile virus was detected in south africa in 2010 in a mare and her aborted fetus; previously, only lineage 2 west nile virus had been detected in horses and humans in south africa. a 2007 fatal case in a killer whale in texas broadened the known host range of west nile virus to include cetaceans. omsk haemorrhagic fever virus appears to have evolved within the last 1000 years. the viral genomes can be divided into 2 clades — a and b. clade a has five genotypes, and clade b has one. these clades separated about 700 years ago. this separation appears to have occurred in the kurgan province. clade a subsequently underwent division into clade c, d and e 230 years ago. clade c and e appear to have originated in the novosibirsk and omsk provinces, respectively. the muskrat ondatra zibethicus, which is highly susceptible to this virus, was introduced into this area in the 1930s. taxonomy species in the genus flavivirus there are 53 defined species: apoi virus aroa virus bagaza virus banzi virus bouboui virus bukalasa bat virus cacipacore virus carey island virus cowbone ridge virus dakar bat virus dengue virus edge hill virus entebbe bat virus gadgets gully virus ilheus virus israel turkey meningoencephalomyelitis virus japanese encephalitis virus jugra virus jutiapa virus kadam virus kedougou virus kokobera virus koutango virus kyasanur forest disease virus langat virus louping ill virus meaban virus modoc virus montana myotis leukoencephalitis virus murray valley encephalitis virus ntaya virus omsk hemorrhagic fever virus phnom penh bat virus powassan virus rio bravo virus royal farm virus saboya virus saint louis encephalitis virus sal vieja virus san perlita virus saumarez reef virus sepik virus tembusu virus tick-borne encephalitis virus tyuleniy virus uganda s virus usutu virus wesselsbron virus west nile virus yaounde virus yellow fever virus yokose virus zika virus sorted by vector list of species and strains of flavivirus by vector phylogenetic tree of flavivirus with vectors; tick-borne (black), mosquito-borne (purple), with no known vector (red), invertebrate viruses (blue/green) species and strains sorted by vectors: tick-borne viruses distribution of tick-borne encephalitis virus (tbev), kyasanur forest disease virus (kfdv), omsk hemorrhagic fever virus (ohfv), powassan virus (powv), and louping-ill virus (liv) mammalian tick-borne virus group greek goat encephalitis virus (ggev) kadam virus (kadv) krasnodar virus (krdv) mogiana tick virus (mgtv) ngoye virus (ngov) sokuluk virus (sokv) spanish sheep encephalomyelitis virus (ssev) turkish sheep encephalitis virus (tse) tick-borne encephalitis virus serocomplex absettarov virus deer tick virus (dt) gadgets gully virus (ggyv) karshi virus kyasanur forest disease virus (kfdv) alkhurma hemorrhagic fever virus (alkv) langat virus (lgtv) louping ill virus (liv) omsk hemorrhagic fever virus (ohfv) powassan virus (powv) royal farm virus (rfv) tick-borne encephalitis virus (tbev) seabird tick-borne virus group kama virus (kamv) meaban virus (meav) saumarez reef virus (srev) tyuleniy virus (tyuv) mosquito-borne viruses without known vertebrate host cell fusing clade aedes flavivirus cell fusing agent virus aedes galloisi flavivirus barkedji virus calbertado virus chaoyang virus culex flavivirus culex theileri flavivirus spanish culex flavivirus wang thong virus culiseta flavivirus donggang virus hanko virus ochlerotatus caspius flavivirus spanish ochlerotatus flavivirus ilomantsi virus kamiti river virus lammi virus marisma mosquito virus nakiwogo virus nhumirim virus nienokoue virus nounané virus palm creek virus panmunjeom flavivirus quang binh virus yunnan culex flavivirus aroa virus group aroa virus (aroav) bussuquara virus (bsqv) iguape virus (iguv) naranjal virus (njlv) dengue virus group dengue virus (denv) kedougou virus (kedv) japanese encephalitis virus group cacipacore virus (cpcv) koutango virus (kouv) kunjin virus ilheus virus (ilhv) japanese encephalitis virus (jev) murray valley encephalitis virus (mvev) alfuy virus st. louis encephalitis virus (slev) usutu virus (usuv) west nile virus (wnv) yaounde virus (yaov) kokobera virus group kokobera virus (kokv) new mapoon virus (nmv) stratford virus (strv) ntaya virus group bagaza virus (bagv) baiyangdian virus (bydv) duck egg drop syndrome virus (dedsv) ilheus virus (ilhv) israel turkey meningoencephalomyelitis virus (itv) jiangsu virus (jsv) layer flavivirus ntaya virus (ntav) rocio virus (rocv) sitiawan virus (stwv) t'ho virus tembusu virus (tmuv) spondweni virus group spondweni virus (spov) zika virus (zikv) yellow fever virus group banzi virus (banv) bamaga virus (bgv) bouboui virus (bouv) edge hill virus (ehv) fitzroy river virus jugra virus (jugv) saboya virus (sabv) sepik virus (sepv) uganda s virus (ugsv) wesselsbron virus (wessv) yellow fever virus (yfv) others batu cave virus bukulasa bat virus nanay virus rabensburg virus (rabv) sitiawan virus viruses with no known arthropod vector tamana bat virus (tabv) entebbe virus group entebbe bat virus (entv) sokoluk virus yokose virus (yokv) modoc virus group apoi virus (apoiv) cowbone ridge virus (crv) jutiapa virus (jutv) modoc virus (modv) sal vieja virus (svv) san perlita virus (spv) rio bravo virus group bukalasa bat virus (bbv) carey island virus (civ) dakar bat virus (dbv) montana myotis leukoencephalitis virus (mmlv) phnom penh bat virus (ppbv) rio bravo virus (rbv) non vertebrate viruses assam virus bamaga virus crangon crangon flavivirus cuacua virus donggang virus firefly squid flavivirus gammarus chevreuxi flavivirus gammarus pulex flavivirus karumba virus (krbv) hanko virus haslams creek virus mac peak virus (mcpv) marisma mosquito virus mediterranean ochlerotatus flavivirus menghai flavivirus nakiwogo virus (nakv) nanay virus nounané virus ochlerotatus caspius flavivirus palm creek virus parramatta river virus southern pygmy squid flavivirus soybean cyst nematode virus 5 xishuangbanna aedes flavivirus viruses known only from sequencing aedes flavivirus aedes cinereus flavivirus aedes vexans flavivirus culex theileri flavivirus vaccines time-line of historical highlights of flavivirus research the very successful yellow fever 17d vaccine, introduced in 1937, produced dramatic reductions in epidemic activity. effective inactivated japanese encephalitis and tick-borne encephalitis vaccines were introduced in the middle of the 20th century. unacceptable adverse events have prompted change from a mouse-brain inactivated japanese encephalitis vaccine to safer and more effective second generation japanese encephalitis vaccines. these may come into wide use to effectively prevent this severe disease in the huge populations of asia—north, south and southeast. the dengue viruses produce many millions of infections annually due to transmission by a successful global mosquito vector. as mosquito control has failed, several dengue vaccines are in varying stages of development. cyd-tdv, sold under the trade name dengvaxia, is a tetravalent chimeric vaccine that splices structural genes of the four dengue viruses onto a 17d yellow fever backbone. dengvaxia is approved in five countries. an alternate approach to the development of flavivirus vaccine vectors is based on the use of viruses that infect insects. insect-specific flaviviruses, such as binjari virus, are unable to replicate in vertebrate cells. nevertheless, recombinant viruses in which structural protein genes (prme) of binjari virus are exchanged with those of dengue virus, zika virus, west nile virus, yellow fever virus, or japanese encephalitis virus replicate efficiently in insect cells where high titers of infectious virus particles are produced. immunization of mice with a binjari vaccine bearing the zika virus structural proteins protected mice from disease after challenge. a similar approach employs the insect-specific alphavirus eilat virus as a vaccine platform. ... these new vaccine platforms generated from insect-specific flaviviruses and alphaviruses represent affordable, efficient, and safe approaches to rapid development of infectious, attenuated vaccines against pathogens from these two virus families.