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DENGUE VIRUS TYPE 3 ADAPTIVE CHANGES DURING EPIDEMICS IN SÃO JOSE DE RIO PRETO, BRAZIL, 2006-2007
Autor
Afiliación
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, Brazil
Universidade Estadual Paulista “Júlio de Mesquita Filho”. Faculdade de Ciências Farmacêuticas. Departamento de Ciências Biológicas. Laboratório de Saúde Pública. Araraquara, SP, Brazil
Division of Heath Science and Technology. Massachusetts Institute of Technology. Cambridge, MA, United States of America
Department of Infectious Disease and Global Health. Cummings School of Veterinary Medicine. Tufts University. North Grafton, MA, United States of America
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, SP, Brazil
Faculdade de Medicina de São José do Rio Preto. Laboratório de Pesquisas em Virologia. São José do Rio Preto, SP, Brazil
Universidade Estadual Paulista “Júlio de Mesquita Filho”. Faculdade de Ciências Farmacêuticas. Departamento de Ciências Biológicas. Laboratório de Saúde Pública. Araraquara, SP, Brazil
Division of Heath Science and Technology. Massachusetts Institute of Technology. Cambridge, MA, United States of America
Department of Infectious Disease and Global Health. Cummings School of Veterinary Medicine. Tufts University. North Grafton, MA, United States of America
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, SP, Brazil
Faculdade de Medicina de São José do Rio Preto. Laboratório de Pesquisas em Virologia. São José do Rio Preto, SP, Brazil
Resumen en ingles
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.
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