Abstract

The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998–2000) and BR3 (2003–05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue.

Highlights

  • IntroductionThe four serotypes of dengue virus (DENV 1–4) (family Flaviviridae, genus Flavivirus) are antigenically and genetically distinct

  • The four serotypes of dengue virus (DENV 1–4) are antigenically and genetically distinct

  • Our study demonstrates that the isolates from Sao Josedo Rio Preto (SJRP)/SP all group within the American/Asian genotype together with isolates from South and Central America and the Caribbean, as previously demonstrated for other Brazilian isolates [21,22;44]

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Summary

Introduction

The four serotypes of dengue virus (DENV 1–4) (family Flaviviridae, genus Flavivirus) are antigenically and genetically distinct. DENV has a single-stranded positive-sense RNA genome of 10,700 nucleotides surrounded by a nucleocapsid and covered by a lipid envelope containing viral glycoproteins. Phylogenetic analyses of dengue virus type 2 (DENV-2) based on the envelope gene has revealed the existence of six genotypes: (i) Asian I, (ii) Asian II, (iii) Cosmopolitan, (iv) American, (v) American/Asian and (vi) sylvatic [5,6,7]. Following the introduction of the American/Asian genotype to the American continent, likely from Vietnam into Cuba, the first case of Dengue hemorrhagic fever was reported in the Americas in 1981 [8]. The American/Asian genotype has been responsible for the displacement of less virulent strains of the American genotype from many regions of the Americas and caused major epidemics with increased pathogenicity on this continent [9,10,11]

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