title: Dengue virus type 3 adaptive changes during epidemics in São Jose de Rio Preto, Brazil, 2006-2007.
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 São José 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.
authors.affiliation: Laboratório de Evolução Molecular e Bioinformática (LEMB), Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Christian Julian
authors.initials: CJ
authors.lastname: Villabona-Arenas
authors.forename: Adriano
authors.initials: A
authors.lastname: Mondini
authors.forename: Irene
authors.initials: I
authors.lastname: Bosch
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Schimdt
authors.forename: Diane
authors.initials: D
authors.lastname: Schimitt
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Calzavara-Silva
authors.forename: Paolo M de A
authors.initials: PM
authors.lastname: Zanotto
authors.forename: Maurício L
authors.initials: ML
authors.lastname: Nogueira
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D001483:Base Sequence; D001499:Bayes Theorem; D001938:Brazil / Q000453:epidemiology; D003062:Codon / Q000235:genetics; D003715:Dengue / Q000453:epidemiology* / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D058872:Epidemics; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D010802:Phylogeny
chemical_list: D003062:Codon