Spatiotemporal dynamics of DENV-2 Asian-American genotype lineages in the Americas

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 1990 s, lineage III becomes the prevalent DENV-2 one in the Caribbean and South America during the 1990 s, 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.

Figure 1. ML tree of 1,932 DENV-2 E gene sequences circulating globally.

DENV-2 genotypes (Sylvatic, American, Asian I and II, Cosmopolitan and Asian/American) are identified. For visual clarity, strains from each genotype are shown collapsed. Only aLTR support values of major branching are shown. All horizontal branch lengths are drawn to a scale of nucleotide substitutions per site.

Figure 2. Spatiotemporal dynamics of dissemination of DENV-2 AS/AM genotype in the Americas.

Viral dispersal pattern between 1984 and 2009. Lines between locations represent branches in the Bayesian MCC tree along which location transitions occurs. The color of lines informs the date of the earliest viral migrations among each pair of locations. (BO-PY: Bolivia–Paraguay, BRN–BRNE: Brazil Northern-Brazil Northeastern, BRSE: Brazil Southeastern, CAM: Central America-Mexico, CO-EC: Colombia-Ecuador, GA: Greater Antilles, LA: Lesser Antilles, NI: Nicaragua, PE: Peru, VE: Venezuela)

Figure 3. Major estimated viral migration rates among locations as measured using ‘Markov jump’ counts.

The width of the arrows is proportional to the viral transitions rate. Transition rates lower than 0.1 were excluded for clarity. (CAM: Central America-Mexico, GA: Greater Antilles, LA: Lesser Antilles, PE: Peru, SA-1: South America 1, SA-2: South America 2)

Figure 4. Time-scaled Bayesian Maximum Clade Credibility tree for the DENV-2 AS-AM genotype.

Four major highly supported monophyletic clades (I-IV) are identified. Branches are colored according to the most probable location (legend shown on the left side) of their parental node inferred by discrete phylogeographical analysis. For visual clarity, clades III and IV has been collapsed (see Fig.5 and Fig.6). PP values >0.90 at key nodes are represented by (*). All horizontal branch lengths are drawn to a scale of years. The tree is automatically rooted under the assumption of a relaxed molecular clock. (CO-EC: Colombia-Ecuador, LA: Lesser Antilles, GA: Greater Antilles)

Figure 5. Time-scaled Bayesian Maximum Clade Credibility sub-tree corresponding to the Clade III.

Three major highly supported monophyletic clades: III-PR, III-LA and III-SA are identified within clade III. For further details see legend of Fig 4. (CO-EC: Colombia-Ecuador, LA: Lesser Antilles, GA: Greater Antilles, PE: Peru, BRSE: Brazil Southeastern, BRN–BRNE: Brazil Northern-Brazil Northeastern, VE: Venezuela, BO-PY: Bolivia-Paraguay)

Figure 6. Time-scaled Bayesian Maximum Clade Credibility sub-tree corresponding to the Clade IV.

Five major highly supported monophyletic clades: IV-SA_1–4 and IV-CAM are identified within clade IV. For further details see legend of Fig 4. (CO-EC: Colombia-Ecuador, LA: Lesser Antilles, GA: Greater Antilles, PE: Peru, BRSE: Brazil Southeastern, BRN–BRNE: Brazil Northern-Brazil Northeastern, VE: Venezuela, BO-PY: Bolivia-Paraguay, NI: Nicaragua, CAM: Central America-Mexico)

Figure 7. Distribution of DENV-2 AS/AM genotype sequences isolated in Puerto Rico (n = 195), Brazil (n = 77), Venezuela/Colombia (n = 64), and Peru (n = 38) at different time periods across the major phylogenetic lineages.