Abstract
Dengue virus (DENV) is a flavivirus responsible for the most common and burdensome arthropod-borne viral disease of humans[1]. DENV evolution has been extensively studied on broad geographic and time scales, using sequences from a single gene[2,3]. It is believed that DENV evolution in humans is dominated primarily by purifying selection due to the constraint of maintaining fitness in both humans and mosquitoes[4,5]. Few studies have explored DENV evolutionary dynamics using whole genome sequences, nor have they explored changes in viral diversity that occur during intra-epidemic periods. We used deep sequencing of the viral coding region to characterize DENV-1 evolution in a Colombian population sampled during two high-prevalence dengue seasons in which serotype dominance shifted. Our data demonstrate patterns of strain extinction and replacement within DENV-1 as its prevalence waned and DENV-3 became established. A comparison of whole-genome versus single-gene-based phylogenetic analyses highlights an important difference in evolutionary patterns. We report a trend of higher nonsynonymous to synonymous diversity ratios among non-structural (NS) genes, and statistically significantly higher values among these ratios in the NS1 gene after DENV-1 strain replacement. These results suggest that positive selection could be driving DENV evolution within individual communities. Signals of positive selection coming from distinct samples may be drowned out when combining multiple regions with differing patterns of endemic transmission as commonly done by large-scale geo-temporal assessments. Here, we frame our findings within a small, local transmission history which aids significance. Moreover, these data suggest that the NS1 gene, rather than the E gene, may be a target of positive selection, although not mutually exclusive, and potentially useful sentinel of adaptive changes at the population level.
Highlights
Dengue virus (DENV; Flaviviridae; Flavivirus) is the cause of the most common and most important arthropod-borne viral disease of humans
Samples involved in this study were chosen from among dengue-suspected human serum specimens collected as part of standard diagnostic activities of the Eliminate Dengue Program in Colombia (IRB #24020 approved by Comitede Bioetica de Investigacion en Humanos de la Sede de Investigacion Universitaria CBE-SIU, Universidad de Antioquia 2016)
Our study period was characterized by an abundance of DENV-1 infections throughout 2014, an inter-epidemic period in 2015, and a decline in DENV-1 prevalence during a rise in DENV-3 prevalence throughout 2016 (Fig 1)
Summary
Dengue virus (DENV; Flaviviridae; Flavivirus) is the cause of the most common and most important arthropod-borne viral disease of humans. Ae. aegypti populations have reestablished themselves in the Americas since the cessation of eradication programs in the 1970s, and currently these mosquitoes can be found from the southern United States to north of the Southern Cone [1,8]. This expanding range increasingly potentiates DENV transmission in the United States. Reinfection with a different DENV serotype can lead to unusually severe and potentially fatal disease[11,12]. This is worrisome because co-circulation of multiple DENV serotypes has been increasingly reported within endemic areas[8], raising concern that more patients could develop severe disease
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