Dengue Virus Type 3 Adaptive Changes during Epidemics in Sao Jose de Rio Preto, Brazil, 2006–2007
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Author(s) • • • • • •
Villabona-Arenas, Christian Julian
Mondini, Adriano
Bosch, Irene
Schimitt, Diane
Calzavara-Silva, Carlos E.
de A Zanotto, Paolo M.
Nogueira, Mauricio Lacerda
Date Issued
May 2013
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Villabona-Arenas, Christian Julian, Adriano Mondini, Irene Bosch, Diane Schimitt, Carlos E. Calzavara-Silva, Paolo M. de A Zanotto, and Maurício L. Nogueira. “Dengue Virus Type 3 Adaptive Changes during Epidemics in São Jose de Rio Preto, Brazil, 2006–2007.” Edited by Amit Kapoor. PLoS ONE 8, no. 5 (May 7, 2013): e63496.
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Final published version
Abstract
Global dengue virus spread in tropical and sub-tropical regions has become a major international public health concern. It is evident that DENV genetic diversity plays a significant role in the immunopathology of the disease and that the identification of polymorphisms associated with adaptive responses is important for vaccine development. The investigation of naturally occurring genomic variants may play an important role in the comprehension of different adaptive strategies used by these mutants to evade the human immune system. In order to elucidate this role we sequenced the complete polyprotein-coding region of thirty-three DENV-3 isolates to characterize variants circulating under high endemicity in the city of Sao Jose de Rio Preto, Brazil, during the onset of the 2006-07 epidemic. By inferring the evolutionary history on a local-scale and estimating rates of synonymous (dS) and nonsynonimous (dN) substitutions, we have documented at least two different introductions of DENV-3 into the city and detected 10 polymorphic codon sites under significant positive selection (dN/dS > 1) and 8 under significant purifying selection (dN/dS < 1). We found several polymorphic amino acid coding sites in the envelope (15), NS1 (17), NS2A (11), and NS5 (24) genes, which suggests that these genes may be experiencing relatively recent adaptive changes. Furthermore, some polymorphisms correlated with changes in the immunogenicity of several epitopes. Our study highlights the existence of significant and informative DENV variability at the spatio-temporal scale of an urban outbreak.
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Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0063496