Circulation of Different Lineages of Dengue Virus Type 2 in Central America, Their Evolutionary Time-Scale and Selection Pressure Analysis

Abstract

Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co-circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV-2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes.

Phylogenetic Analysis of Dengue Virus Types 1 and 4 Circulating in Puerto Rico and Key West, Florida, during 2010 Epidemics

“…Long-term epidemiologic and in vitro studies are needed to determine if strains from the new DENV lineage circulating in Puerto Rico have increased fitness in comparison with older strains, and how this fitness may contribute to the already complex epidemiology of DENV on the island. In summary, our results on the molecular epidemiology of DENV-1 and DENV-4 in Puerto Rico and Florida during 2010 support the notion that an exchange of DENV strains occurrs within the Caribbean islands and between the Caribbean region and other dengue-endemic countries in Central and South America, [18][19][20][21][22] and that these strains and lineages circulating may have an impact on the clinical outcome of dengue cases in the region. …”

Phylogeography and Molecular Epidemiology of an Epidemic Strain of Dengue Virus Type 1 in Sri Lanka

“…The dN/dS (ω) ratio across the viral ORF in our dataset of all viruses used in the above phylogenetic trees was 0.0640 using the single likelihood ancestor (SLAC) method, suggesting that DENV-1 is under strong purifying selection, which has been previously observed for other DENV strains and arboviruses. [36][37][38] Gene-by-gene analysis also revealed strong purifying selection within each protein-coding gene (Table 1). We discuss the effect that it might have had on our phylogenetic trees below.…”

Lineage II of Southeast Asian/American DENV-2 is Associated with a Severe Dengue Outbreak in the Peruvian Amazon

“…36,51,58 Notably, although other lineage/genotype replacement events associated with increased disease severity involved a period of lineage/genotype cocirculation, the southeast Asian/American lineage II viruses from our study were introduced into Loreto in the absence of any DENV-2 competitors. 59,60 It is clear that both host and viral factors can play a role in determining dengue disease severity. Our results indicate that the large number of severe dengue cases observed during the 2010 and 2011 Loreto outbreak was not associated with increased viral replication in human mo-DCs or dissemination in mosquitoes.…”