title: Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage.
abstract: BACKGROUND
  Zika virus (ZIKV) is a mosquito-borne flavivirus distributed throughout much of Africa and Asia. Infection with the virus may cause acute febrile illness that clinically resembles dengue fever. A recent study indicated the existence of three geographically distinct viral lineages; however this analysis utilized only a single viral gene. Although ZIKV has been known to circulate in both Africa and Asia since at least the 1950s, little is known about the genetic relationships between geographically distinct virus strains. Moreover, the geographic origin of the strains responsible for the epidemic that occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010 pediatric case in Cambodia, has not been determined.
  
  
  RESULTS
  To elucidate the genetic relationships of geographically distinct ZIKV strains and the origin of the strains responsible for the 2007 outbreak on Yap Island and a 2010 Cambodian pediatric case of ZIKV infection, the nucleotide sequences of the open reading frame of five isolates from Cambodia, Malaysia, Nigeria, Uganda, and Senegal collected between 1947 and 2010 were determined. Phylogenetic analyses of these and previously published ZIKV sequences revealed the existence of two main virus lineages (African and Asian) and that the strain responsible for the Yap epidemic and the Cambodian case most likely originated in Southeast Asia. Examination of the nucleotide and amino acid sequence alignments revealed the loss of a potential glycosylation site in some of the virus strains, which may correlate with the passage history of the virus.
  
  
  CONCLUSIONS
  The basal position of the ZIKV strain isolated in Malaysia in 1966 suggests that the recent outbreak in Micronesia was initiated by a strain from Southeast Asia. Because ZIKV infection in humans produces an illness clinically similar to dengue fever and many other tropical infectious diseases, it is likely greatly misdiagnosed and underreported.
authors.affiliation: Institute for Human Infections and Immunity, Center for Tropical Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA. adhaddow@gmail.com
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Haddow
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Schuh
authors.forename: Chadwick Y
authors.initials: CY
authors.lastname: Yasuda
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Kasper
authors.forename: Vireak
authors.initials: V
authors.lastname: Heang
authors.forename: Rekol
authors.initials: R
authors.lastname: Huy
authors.forename: Hilda
authors.initials: H
authors.lastname: Guzman
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000349:Africa / Q000453:epidemiology; D000818:Animals; D001208:Asia / Q000453:epidemiology; D016000:Cluster Analysis; D005838:Genotype; D006801:Humans; D008849:Micronesia / Q000453:epidemiology; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058974:Phylogeography; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D000071244:Zika Virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D000071243:Zika Virus Infection / Q000453:epidemiology / Q000821:virology*
chemical_list: D012367:RNA, Viral