Molecular evolution and phylogeny of dengue type 4 virus in the caribbean

Abstract

We sequenced the E gene and adjacent prM/M and NS1 junctions (1940 bp) of 48 Dengue-4 (DEN-4) isolates collected between 1981 and 1999 from 8 Caribbean islands and from 7 South and Central American countries. Phylogenetic analysis confirms a single introduction in the early 1980s and a high degree of gene flow resulting in a pattern of evolution defined more by time period than geographic origin, especially within the Caribbean basin. A modern Caribbean clade consisting of four distinct lineages has arisen, comprised of isolates from Caribbean islands and nearby regions of South America. This clade is defined by three amino acid substitutions in the E (aa 163 and 351) and NS1 (aa 52) proteins. These findings highlight the importance of migration and gene flow in dengue viral change and suggest that efforts to understand disease dynamics in the Caribbean basin need to focus at regional, rather than local scales.

Invasion and Maintenance of Dengue Virus Type 2 and Type 4 in the Americas

“…Finally, the phylogenetic data suggest that both DENV-2 and DENV-4 have evolved in situ in the Americas without multiple introductions from other regions after 1981 (12,13). This is in contrast to the findings of recent studies on DENV-1 in the Pacific, where there were repeated introductions from Southeast Asia (2).…”

“…However, as the majority of DENV-2 subtype III E gene sequences consisted of 1,404 bp, longer sequences were trimmed to this length. Previous studies revealed no evidence of recombination in these data (4,12,13). In total, this resulted in data sets of 89 taxa representing 21 countries for DENV-2 and 62 taxa representing 16 countries in the case of DENV-4 (see Table S1 in the supplemental material).…”

“…By the late 1990s it was suggested that DENV-2 subtype III had displaced the American subtype V in regions where the two might compete (8), although the latter clearly has refugia in some regions of South and Central America (12,46) and is probably more widespread but goes unreported due to an association with mild disease only (46). More recently, the spread of DENV-2 and DENV-4 in the Americas has been investigated through phylogenetic analysis (12,13). This revealed a high degree of gene flow and temporally structured lineages, with any geographic patterning present most likely reflecting the strength of economic and cultural ties, which (in addition to geographic distance) influence the amount of viral movement among countries (12,13).…”

“…More recently, the spread of DENV-2 and DENV-4 in the Americas has been investigated through phylogenetic analysis (12,13). This revealed a high degree of gene flow and temporally structured lineages, with any geographic patterning present most likely reflecting the strength of economic and cultural ties, which (in addition to geographic distance) influence the amount of viral movement among countries (12,13).…”

A secondary dengue 4 infection in a traveler returning from Haiti confirmed by virus isolation, complete genome sequencing and neutralisation assay: A brief report

“…1). This patient was infected with a DEN-4 strain belonging to the genotype IIb, which is most closely related to human strains isolated in 1994 in Puerto Rico (98% identity at the nucleotide level) [12].…”