Dengue fever (DF) is caused by four related DENV-1 to DENV-4 serotype viruses. Each serotype comprises distinct genotypes and lineages, which differ in geographical distribution. The last major outbreak in Mexico occurred between 2012 and 2013 when 112,698 confirmed cases were reported. In these years, although the four serotypes circulated, (DENV-1 and DENV-2 were predominant). To describe the dynamics of this outbreak, we analyzed 396 DENV-1 and 248 DENV-2 serum samples from DENV acute clinical cases from 13 Mexican states. Partial E, NS2A, and NS5 genes were sequenced, mutations were identified, and their genetic variability estimated, along with their evolutionary relationship with DENVV sequences sampled globally. Our DENV-1 and DENV-2 sequences grouped with the genotype V and Asian-American genotype, respectively, suggesting that these genotypes were the only circulating genotypes during the outbreak. Mutations in NS2A and NS5 proteins were widely disseminated throughout the country and suggested the local emergence of new lineages. Based on the phylogeographic analysis, the viral spread was reconstructed, suggesting that coastal regions of the country and tourist destinations such as Yucatan and Quintana Roo played important roles in the dissemination of these lineages.
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