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Intra-host genetic diversity of dengue virus type 4 strains from the municipality of Guarujá,

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Ayda Susana Ortiz Baez
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Paolo Marinho de Andrade Zanotto; Maria Luisa Barbosa; Edison Luiz Durigon; Daniel José Galafasse Lahr
Advisor: Paolo Marinho de Andrade Zanotto

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 viral pathogen. The extent to which viral diversity accrues in infected host influences aspects such as pathogenesis, transmission, and host immunity. Although there are several studies about intra-host genetic diversity in dengue, so far nothing has been revealed about DENV-4. 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. 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 characterized the genetic variability of DENV-4 at different levels, and the forces shaping this diversity. Likewise, we explored major transmission events among DENV-4 variants. Our results revealed a low intra-host genetic diversity for DENV-4. However, we found selective and mutational pressures contributing to genetic diversity, while recombination did not seem play an important role. We further identified purifying selection at population level but sites subject to potential diversifying selection. Additionally, we observed low frequency haplotypes being transmitted among hosts and contributing to the viral diversity of DENV-4 circulating in Guarujá. Our findings provide preliminary insights for future studies in mixed infections, drug resistance, virus variant spread and immune scape. This study is the first effort to investigate the intra-host diversity of DENV-4. (AU)