title: Emergence of the Asian 1 genotype of dengue virus serotype 2 in viet nam: in vivo fitness advantage and lineage replacement in South-East Asia.
abstract: A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Thi Ty Hang
authors.initials: TT
authors.lastname: Vu
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Veasna
authors.initials: V
authors.lastname: Duong
authors.forename: Thien Quy
authors.initials: TQ
authors.lastname: Nguyen
authors.forename: Tinh Hien
authors.initials: TH
authors.lastname: Tran
authors.forename: Michael
authors.initials: M
authors.lastname: Quail
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Jane
authors.initials: J
authors.lastname: Cardosa
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.forename: Niall J
authors.initials: NJ
authors.lastname: Lennon
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Henn
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
mesh_terms: D000293:Adolescent; D001210:Asia, Southeastern / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000453:epidemiology* / Q000821:virology*; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics; D014766:Viremia
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins