Abstract

BackgroundDengue 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.ResultsPhylogenetic 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 × 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.ConclusionsA 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.

Highlights

  • Dengue virus (DENV) is a member of the genus Flavivirus of the family Flaviviridae

  • Genetic variability of DENV-3 genotype III circulating in Venezuela In order to gain insight into the degree of genetic variability of DENV-3 genotype III strains circulating in Venezuela, 29 Venezuelan DENV-3 genotype III E gene sequences representing strains isolated between 2000 and 2007 in seven different Venezuelan geographic locations, were aligned with 58 sequences from DENV-3 genotype III E gene of DENV isolated in Latin America and 11 DENV-3 sequences from strains isolated elsewhere representing other DENV-3 genotypes

  • The phylogenetic analysis presented in these studies reveal an in situ evolution of DENV-3 genotype III following its introduction in the Latin American region, where three different genetic clusters can be observed in DENV-3 genotype III strains circulating in the South American region (Figure 1)

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Summary

Introduction

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. There is a dramatic emergence of DENV-3 genotype III in Latin America. 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. Dengue virus (DENV) is a member of the genus Flavivirus of the family Flaviviridae. Dengue viruses are comprised of four distinct serotypes DENV-4), which are transmitted to humans through the bites of two mosquito species: Aedes aegypti and Aedes albopictus [2]. There is a dramatic re-emergence of DENV in

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