Characterizing intra-host genetic variability in dengue virus (DENV) virus is paramount for understanding its evolution and population dynamics in the context of its current status as a major human pathogen. The extent to which viral diversity accrues in infected hosts influences aspects such as pathogenesis, transmission, and host immunity. Although there are several studies about intra-host genetic diversity in dengue, limited amount of data has been reported for DENV-4 so far. In the Guarujá Municipality in the State of São Paulo, the reemergence and spread of this serotype was associated with its co-circulation and the displacement of serotypes 1, 2 and 3 during recent outbreaks (Villabona-Arenas et al., PLoS NTD in Press). Based on this epidemiological framework, we seek to identify the intra-host genetic variation of DENV-4 strains from samples collected during the 2013 outbreak by using deep sequencing technologies. We will estimate the level of variability and the evolutionary history of these viruses in response to selective pressures imposed by an urban population previously exposed to the remaining three dengue serotypes. This study would also be the first effort to investigate the intra-host diversity of DENV-4.
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