Phylogeography and molecular evolution of dengue 2 in the Caribbean basin, 1981–2000

Abstract

We sequenced the envelope (E) genes of 59 DEN-2 isolates collected from ten Caribbean islands, six South American countries, and two Central American countries between 1981 and 2000, a period characterized by hyperendemicity and increased incidence of severe dengue. Fifty-two isolates belonged to "American/Asian" subtype IIIb, possessing a characteristic polar residue at envelope aa position 390 (N [n = 48] or S [n = 4]) common to that group. Six isolates from Trinidad (1981), Honduras (1991 [4]), and El Salvador (1987) fell into the "Native American" subtype V (D at aa 390), and one from Honduras (1986) belonged to "Asian" subtype I. The data suggest that after its first isolation in the Caribbean in 1981, genotype IIIb spread throughout the Americas and effectively replaced subtype V throughout the Caribbean basin. The strain also evolved into several distinct lineages, based on substitutions in the E glycoprotein (amino acids 91 and 131), two of which were still in circulation in 2000. Interestingly, a molecular clock did not fit the data well, suggesting that other sources of rate variation, such as differential selection or differences in effective population sizes, may exist among lineages. Our results indicate the importance of large temporal- and geographical-scale phylogenetic studies in understanding disease dynamics, particularly where replacements between regions can occur.

Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok

“…At the phylogenetic level, each viral serotype is subdivided into a number of distinct clades (such as genotypes) that have differing frequencies within populations and experience episodes of extinction and replacement (19)(20)(21)(22)(23). What causes these disjunct phylogenetic patterns is unclear, although the lack of definitive evidence for fitness differences among strains has led most workers to conclude that clade extinction results from random population bottlenecks and stochastic fadeout (20,22,(24)(25)(26).…”

“…What causes these disjunct phylogenetic patterns is unclear, although the lack of definitive evidence for fitness differences among strains has led most workers to conclude that clade extinction results from random population bottlenecks and stochastic fadeout (20,22,(24)(25)(26). We analyzed gene sequence data for all DENV serotypes circulating in Bangkok during the period 1973-2002 (see Methods) and found a concordance between episodes of clade extinction and changing levels of serotype abundance, with this process occurring on an Ϸ10-year time scale (Fig.…”

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

“…Compared to that of DENV-4, the progress of DENV-2 subtype III following its introduction was less easy to track, since serological testing would not have distinguished between the old (subtype V) and the new strains. 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).…”

“…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).…”

Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

“…Rico-Hesse et al (16) analyzed two DEN-2 viruses isolated in Venezuela and Colombia some time around 1987, and concluded that they belonged to the Southeast Asian genotype. In Brazil, this genotype was probably introduced either at the same time or at some point during 1988, like in other areas of the Americas (6,8,16,18,20,38,40).…”