Circulation of Different Lineages of Dengue Virus Type 2 in Central America, Their Evolutionary Time-Scale and Selection Pressure Analysis

Germán Añez,Maria E Morales-Betoulle,Maria Rios,Lark L Coffey

doi:10.1371/journal.pone.0027459

Germán Añez, Maria E Morales-Betoulle + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0027459

Copy DOI

Abstract

Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co-circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV-2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes.

Highlights

Dengue, the most common arboviral disease in the world, is caused by any of the four serotypes of dengue virus (DENV-1 to 4), genus Flavivirus, family Flaviviridae
Phylogenetic analysis of DENV-2 E protein gene and open reading frame To study the phylogenetic relationships between the strains of DENV-2 circulating in Central America, a search for strains from its constituent countries was conducted in the GenBank database
From Central America, most of the DENV strains deposited in the database were from Nicaragua, from where we retrieved a total of 181 complete genome sequences of DENV-2 spanning from 1999 to 2009

Summary

Introduction

The most common arboviral disease in the world, is caused by any of the four serotypes of dengue virus (DENV-1 to 4), genus Flavivirus, family Flaviviridae. DENV was first isolated in the Americas in 1953 and the disease has been present in Central America since 1978, when epidemics caused by DENV-1 were reported in Belize, Guatemala, El Salvador and Honduras [6]. Central America is the isthmian portion of the American continent constituted by Belize, Costa Rica, Guatemala, Honduras, El Salvador, Nicaragua and Panama. Dengue is hyperendemic in Central America as well as in most of the countries of the continent, especially after the re-introduction of DENV-3 in the 90s [9]. Between 1999 and 2010, more than 700,000 cases of dengue have been reported in Central America, .24,000 of which correspond to severe dengue (formerly, dengue hemorrhagic fever) with 468 fatalities, according to data submitted by the countries to the Pan American Health Organization [10] (Figures S1, S2, and S3)

Methods

Results

Conclusion