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. 2012 Mar;12(2):332-44.
doi: 10.1016/j.meegid.2011.12.005. Epub 2011 Dec 17.

Population structure of the dengue viruses, Aragua, Venezuela, 2006-2007. Insights into dengue evolution under hyperendemic transmission

Rosmari Rodriguez-Roche  1 , Elci Villegas, Shelley Cook, Pauline A W Poh Kim, Yoandri Hinojosa, Delfina Rosario, Iris Villalobos, Herminia Bendezu, Martin L Hibberd, Maria G Guzman
Affiliations

Population structure of the dengue viruses, Aragua, Venezuela, 2006-2007. Insights into dengue evolution under hyperendemic transmission

Rosmari Rodriguez-Roche et al. Infect Genet Evol. 2012 Mar.

Abstract

During the past three decades there has been a notable increase in dengue disease severity in Venezuela. Nevertheless, the population structure of the viruses being transmitted in this country is not well understood. Here, we present a molecular epidemiological study on dengue viruses (DENV) circulating in Aragua State, Venezuela during 2006-2007. Twenty-one DENV full-length genomes representing all of the four serotypes were amplified and sequenced directly from the serum samples. Notably, only DENV-2 was associated with severe disease. Phylogenetic trees constructed using Bayesian methods indicated that only one genotype was circulating for each serotype. However, extensive viral genetic diversity was found in DENV isolated from the same area during the same period, indicating significant in situ evolution since the introduction of these genotypes. Collectively, the results suggest that the non-structural (NS) proteins may play an important role in DENV evolution, particularly NS1, NS2A and NS4B proteins. The phylogenetic data provide evidence to suggest that multiple introductions of DENV have occurred from the Latin American region into Venezuela and vice versa. The implications of the significant viral genetic diversity generated during hyperendemic transmission, particularly in NS protein are discussed and considered in the context of future development and use of human monoclonal antibodies as antivirals and tetravalent vaccines.

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Figures

Fig. 1
Fig. 1
Bayesian phylogeny of DENV-1 polyprotein nucleotide data set, including Venezuelan isolates from 2006 to 2007. For clarity, posterior probabilities obtained via Bayesian methods are shown for the main clades only. Bootstrap support values obtained via 1000 neighbour-joining replicates were similarly high for these nodes. All horizontal branch lengths are drawn to scale; bar, 0.02 substitutions per site. The tree is midpoint-rooted for purposes of clarity only. The asterisks (∗) indicate those DENV sequences that are published for the first time in the current study.
Fig. 2
Fig. 2
Bayesian phylogeny of the DENV-2 polyprotein nucleotide data set, including Venezuelan isolates from 2006 to 2007. For clarity, posterior probabilities obtained via Bayesian methods are shown for the main clades only. Bootstrap support values obtained via 1000 neighbour-joining replicates were similarly high for these nodes. All horizontal branch lengths are drawn to scale; bar, 0.02 substitutions per site. The tree is midpoint-rooted for purposes of clarity only. The asterisks (∗) indicate those DENV sequences that are published for the first time in the current study.
Fig. 3
Fig. 3
Bayesian phylogeny of the DENV-3 polyprotein nucleotide data set, including Venezuelan isolates from 2006 to 2007. For clarity, posterior probabilities obtained via Bayesian methods are shown for the main clades only. Bootstrap support values obtained via 1000 neighbour-joining replicates were similarly high for these nodes. All horizontal branch lengths are drawn to scale; bar, 0.3 substitutions per site. The tree is midpoint-rooted for purposes of clarity only. The asterisks (∗) indicate those DENV sequences that are published for the first time in the current study.
Fig. 4
Fig. 4
Bayesian phylogeny of the DENV-4 polyprotein nucleotide data set, including Venezuelan isolates from 2006 to 2007. For clarity, posterior probabilities obtained via Bayesian methods are shown for the main clades only. Bootstrap support values obtained via 1000 neighbour-joining replicates were similarly high for these nodes. All horizontal branch lengths are drawn to scale; bar, 0.4 substitutions per site. The tree is midpoint-rooted for purposes of clarity only. The asterisks (∗) indicate those DENV sequences that are published for the first time in the current study.
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