Worldwide spread of Dengue virus type 1

Abstract

Background: DENV-1 is one of the four viral serotypes that causes Dengue, the most common mosquito-borne viral disease of humans. The prevalence of these viruses has grown in recent decades and is now present in more than 100 countries. Limited studies document the spread of DENV-1 over the world despite its importance for human health.

Methodology/principal findings: We used representative DENV-1 envelope gene sequences to unravel the dynamics of viral diffusion under a Bayesian phylogeographic approach. Data included strains from 45 distinct geographic locations isolated from 1944 to 2009. The estimated mean rate of nucleotide substitution was 6.56 × 10⁻⁴ substitutions/site/year. The larger genotypes (I, IV and V) had a distinctive phylogenetic structure and since 1990 they experienced effective population size oscillations. Thailand and Indonesia represented the main sources of strains for neighboring countries. Besides, Asia broadcast lineages into the Americas and the Pacific region that diverged in isolation. Also, a transmission network analysis revealed the pivotal role of Indochina in the global diffusion of DENV-1 and of the Caribbean in the diffusion over the Americas.

Conclusions/significance: The study summarizes the spatiotemporal DENV-1 worldwide spread that may help disease control.

Figure 1. Evolutionary history of DENV-1.

The phylogeny was inferred using a Maximum likelihood analysis of 1583 sequences. Because of the large number of isolates branch tips were removed. Numbers correspond to bootstrapping values.

Figure 2. The Phylogenetic relationships of DENV-1 genotypes.

Topologies correspond to Maximum Clade Credibility trees (MCC) for A) Genotype I, B) Genotype IV and C) Genotype V. Because of the large number of isolates branch tips were removed. Major geographical clades are indicated (ISO 3166 Codes). Black numbers correspond to posterior probability estimates and gray numbers correspond to the TMRCAs. Scale bar for years. Triangles represent Thailand isolates and squares represent Indonesia isolates.

Figure 3. The Spread of DENV-1 genotypes.

The likely dispersion routes were estimated from a discrete diffusion phylogeography process for A) Genotype I, B) Genotype IV and C) Genotype V. Dotted lines represent plausible migratory paths. Gray acronyms represent the apparent source of origin for each genotype (ISO 3166 Codes). Grey lines represent inferred introductions by studies with diseased travelers. A location-annotated MCC to KML for visualization over time is available for Google Earth as supporting material.

Figure 4. Network visualization of diffusion of DENV-1 genotypes.

The analysis was done over major geographical areas and integrating migration rates among them as attributes. Thickness gauge at the bar scale for rates.

Figure 5. Demographic history for each genotype.

Overlay of Bayesian skyline plot showing the Ne.g. (product of the effective population size and the generation length) for each DENV-1 genotypes. Ninety-five percent high probability densities (95% HPD) are showed as thin discontinuous lines around each mean plot.