Abstract
The Asian/American (AS/AM) genotype of dengue virus type 2 (DENV-2) has been evolving in the Americas over the last 30 years, leading to several waves of dengue epidemics and to the emergence of different viral lineages in the region. In this study, we investigate the spatiotemporal dissemination pattern of the DENV-2 lineages at a regional level. We applied phylogenetic and phylogeographic analytical methods to a comprehensive data set of 582 DENV-2 E gene sequences of the AS/AM genotype isolated from 29 different American countries over a period of 30 years (1983 to 2012). Our study reveals that genetic diversity of DENV-2 AS/AM genotype circulating in the Americas mainly resulted from one single founder event and can be organized in at least four major lineages (I to IV), which emerged in the Caribbean region at the early 1980s and then spread and die out with different dynamics. Lineages I and II dominate the epidemics in the Caribbean region during the 1980s and early 1990s, lineage III becomes the prevalent DENV-2 one in the Caribbean and South America during the 1990s, whereas lineage IV dominates the epidemics in South and Central America during the 2000s. Suriname and Guyana seem to represent important entry points for DENV-2 from the Lesser Antilles to South America, whereas Venezuela, Brazil and Nicaragua were pointed as the main secondary hubs of dissemination to other mainland countries. Our study also indicates that DENV-2 AS/AM genotype was disseminated within South America following two main routes. The first route hits Venezuela and the western side of the Andes, while the second route mainly hits Brazil and the eastern side of the Andes. The phenomenon of DENV-2 lineage replacement across successive epidemic outbreaks was a common characteristic in all American countries, although the timing of lineage replacements greatly vary across locations.
Highlights
Dengue virus (DENV) is an archetypal emerging and reemerging virus because it is an infection that appears as a new entity in certain areas where none has existed before and resurfaces in places where it already has existed [1]
All dengue virus type 2 (DENV-2) AS/AM genotype sequences of American origin (n = 582) segregate in a highly supported monophyletic sub-group nested within sequences of Asian origin, supporting that current diversity of DENV-2 AS/AM genotype sequences in the Americas mainly resulted from a single founder event
Our analysis confirms that the DENV-2 AS/AM genotype was most probably introduced to the Greater Antilles (GA) and rapidly disseminated to the Lesser Antilles (LA) and the northeastern coast of South America (Suriname [SR] and Guyana [GY])
Summary
Dengue virus (DENV) is an archetypal emerging and reemerging virus because it is an infection that appears as a new entity in certain areas where none has existed before and resurfaces in places where it already has existed [1]. Each of the four DENV serotypes harbor extensive genetic diversity in the form of phylogenetically distinct clusters defined as genotypes and intragenotype lineages that co-circulate with distinctive geographical and temporal patterns [2]. All these layers of viral diversity combined with host genetics and vector biology comprise the matrix responsible for the complex viral transmission dynamics of DENV at a global scale. One of the best documented genotype replacement events occurred in the 1980s when the Asian/American (AS/AM) genotype of DENV-2 was introduced for the first time in the Americas, displacing the local American genotype [4]. Phylogenetic analyses of the AS/AM genotype of DENV-2 in the Americas have identified the circulation of: three distinct clades in Puerto Rico (1986–2007) [11,12] and the Lesser Antilles [13], two lineages in Bolivia (1997–2006) [14], Paraguay (2001–2006) [15] and Peru (1999–2012) [16], up to three lineages in Brazil (1990– 2010) [17,18,19,20] and Colombia (1988–2010) [21], up to six genetic clades in Venezuela (1991–2008) [22,23], and two clades in Mexico (1996–2000) [24] and Central America (1999–2009) [25]
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