Codon adaptation biases among sylvatic and urban genotypes of Dengue virus type 2

Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle.