title: Evolution of dengue virus type 3 genotype III in Venezuela: diversification, rates and population dynamics.
abstract: BACKGROUND
  Dengue virus (DENV) is a member of the genus Flavivirus of the family Flaviviridae. DENV are comprised of four distinct serotypes (DENV-1 through DENV-4) and each serotype can be divided in different genotypes. Currently, there is a dramatic emergence of DENV-3 genotype III in Latin America. Nevertheless, we still have an incomplete understanding of the evolutionary forces underlying the evolution of this genotype in this region of the world. In order to gain insight into the degree of genetic variability, rates and patterns of evolution of this genotype in Venezuela and the South American region, phylogenetic analysis, based on a large number (n = 119) of envelope gene sequences from DENV-3 genotype III strains isolated in Venezuela from 2001 to 2008, were performed.
  
  
  RESULTS
  Phylogenetic analysis revealed an in situ evolution of DENV-3 genotype III following its introduction in the Latin American region, where three different genetic clusters (A to C) can be observed among the DENV-3 genotype III strains circulating in this region. Bayesian coalescent inference analyses revealed an evolutionary rate of 8.48 x 10⁻⁴ substitutions/site/year (s/s/y) for strains of cluster A, composed entirely of strains isolated in Venezuela. Amino acid substitution at position 329 of domain III of the E protein (A→V) was found in almost all E proteins from Cluster A strains.
  
  
  CONCLUSIONS
  A significant evolutionary change between DENV-3 genotype III strains that circulated in the initial years of the introduction in the continent and strains isolated in the Latin American region in recent years was observed. The presence of DENV-3 genotype III strains belonging to different clusters was observed in Venezuela, revealing several introduction events into this country. The evolutionary rate found for Cluster A strains circulating in Venezuela is similar to the others previously established for this genotype in other regions of the world. This suggests a lack of correlation among DENV genotype III substitution rate and ecological pattern of virus spread.
authors.affiliation: Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ramírez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Fajardo
authors.forename: Zoila
authors.initials: Z
authors.lastname: Moros
authors.forename: Marlene
authors.initials: M
authors.lastname: Gerder
authors.forename: Gerson
authors.initials: G
authors.lastname: Caraballo
authors.forename: Daria
authors.initials: D
authors.lastname: Camacho
authors.forename: Guillermo
authors.initials: G
authors.lastname: Comach
authors.forename: Victor
authors.initials: V
authors.lastname: Alarcón
authors.forename: Julio
authors.initials: J
authors.lastname: Zambrano
authors.forename: Rosa
authors.initials: R
authors.lastname: Hernández
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.forename: Juan
authors.initials: J
authors.lastname: Cristina
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Liprandi
mesh_terms: D016000:Cluster Analysis; D003715:Dengue / Q000453:epidemiology* / Q000821:virology*; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014687:Venezuela / Q000453:epidemiology; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: C084188:E protein, Dengue virus type 3; D014759:Viral Envelope Proteins