Evolution of Dengue Virus Type 3 Genotype III in Venezuela: Diversification, Rates and Population Dynamics

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.

Origin and Evolution of Dengue Virus Type 3 in Brazil

“…The phylogenetic analysis presented here confirms that DENV-3 outbreaks occurring in the American continent since the mid-1990s are the result of a single introduction of genotype III. This analysis also suggest that viral introduction probably occurs through Central America or Mexico, and from there the virus spread to the Caribbean and South America following three major routes, giving rise to three independent evolutionary lineages (Caribbean/South America I to III), consistent with previous findings [18], [19], [22]. According to this model, Central American countries and Mexico were the hubs of genotype III spread in the Americas, while the Caribbean region acted as a staging post between Central America/Mexico and South America.…”

Evidence of increasing diversification of Zika virus strains isolated in the American continent

“…Moreover, the rates estimated for ZIKV in this study are roughly similar to the ones estimated for other members of the family Flaviviridae , like Dengue virus (DENV) (E, 0.76 × 10 −3 s/s/y), DENV type 3 genotype III (E, 0.84 × 10 −3 s/s/y), West Nile virus (WNV) (0.50 × 10 −3 s/s/y) …”

“…The mean rate obtained for the ZIKV strains enrolled in these studies is comparatively similar to rates reported for fast evolving RNA viruses, like Human Immunodeficiency Virus type 1 (HIV-1) (PR + RT region; 2.4 × 10 −3 s/s/y) 31 or Ebola virus (full genome, 0.96 × 10 −3 s/s/y). 32 Moreover, the rates estimated for ZIKV in this study are roughly similar to the ones estimated for other members of the family Flaviviridae, like Dengue virus (DENV) (E, 0.76 × 10 −3 s/s/y), 33 DENV type 3 genotype III (E, 0.84 × 10 −3 s/s/y), 34 West Nile virus (WNV) (0.50 × 10 −3 s/s/y). 35 Importantly, contributions of the third codon position to main evolutionary rate (2.394 from a total of 3.0) was found to be significant (Table 1).…”

Ancient Ancestry of KFDV and AHFV Revealed by Complete Genome Analyses of Viruses Isolated from Ticks and Mammalian Hosts

“…This may be explained by the slightly higher NS5 and E diversity in KFDV relative to the rest of the genome (Table 3), however, the limited number of KFDV isolates available for this study might not be fully representative of the extant KFDV diversity. In accordance with the evolutionary rate patterns for vector-borne flaviviruses [21], the AHFV/KFDV rate is slower than mosquito-borne flaviviruses, including Dengue virus (DENV) [22] and yellow fever virus (YFV) [23] and more similar to tick-borne flaviviruses, including the closely related tick-borne encephalitis virus (TBEV Siberian subtype, 1.64×10 −4 sub/site/year) [24]. The evolutionary rate is also similar to that of an unrelated tick-borne member of the Bunyaviridae family, Crimean-Congo hemorrhagic fever virus (0.58–1.52×10 −4 sub/site/year)[25].…”