Dengue virus (DENV) is a flavivirus responsible for the most common and burdensome arthropod-borne viral disease of humans. 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.
|Original language||English (US)|
|State||Published - Mar 2019|
Bibliographical noteFunding Information:
The authors thank Karl Ciuoderis and Carol Mesa from the Program for the Study and Control of Tropical Diseases (PECET) from the Universidad de Antioquia for helping screen and ship samples to Madison, Wisconsin. We also thank the Eliminate Dengue Program (EDP) for setting up the fever clinic which provided us with samples as part of a pilot project conducted in the Barrio Paris of the municipality of Bello, Antioquia. Lastly, a thank you to Dr. Tony Goldberg for all the useful discussions regarding this manuscript.
© 2019 Salvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.