Document details

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus

Author(s): Botosso, Viviane F. ; Zanotto, Paolo M. de A. ; Ueda, Mirthes ; Arruda, Eurico ; Gilio, Alfredo E. ; Ieira, Sandra E. ; Stewien, Klaus E. ; Peret, Teresa C. T. ; Jamal, Leda F. ; Pardini, Maria I. de M. C. ; Pinho, Joãr ; Massad, Duardo ; Sant'Anna, Osvaldo A. ; Holmes, Eddie C. ; Durigon, Edison L. ; Comone, Priscila ; Do Sacramento, Patrícia R. ; Durigan, Mariana S. ; Oliveira, Danielle B. L. ; Moraes, Claudia T. P. ; Campo, Angélica C. A. ; Leal, Andréia L. ; Silva, Tereza S. ; Carvalho, Ariane C. L. ; Tenório, Elisabeth C. N. ; Cintra, Otavio A. L. ; Ansarah-Sobrinho, Camilo ; Proençna-Modena, José L. ; Iwamoto, Marisa A. ; De Paula, Flávia E. ; Souza, Maria C. O. ; Vaz-de-Lima, Lourdes R. A. ; Matsumoto, Tokiko K. ; Sato, Neuza N. ; Salgado, Maristela M. ; Hong, Marisa A. ; Requejo, Henry I. ; Barbosa, Maria L. ; Oliveiveira, Carmem A. F. ; Passos, Saulo D. ; Pecchini, Rogério ; Berezin, Eitan ; Schvartsman, Claudio ; Pannuti, Cláudio S. ; Candeias, João M. G. ; Han, Sang W. ; Garcia, José F. ; Carrilho, Flair J. ; Figueiredo, Luíz T. M. ; Duarte, Alberto J. Da S. ; Wolff, José L. C. ; Rahal, Paula [UNESP] ; Richtzenhain, Leonardo J. ; Gonçales Jr., Fernando L. ; De Lima, Edimo G.

Date: 2014

Persistent ID: http://hdl.handle.net/11449/70883

Origin: Oasisbr

Subject(s): epitope; guanine nucleotide binding protein; virus protein; amino acid substitution; child; codon; controlled study; gene sequence; genotype; human; infant; major clinical study; newborn; nonhuman; nucleotide sequence; phylogeny; preschool child; Respiratory syncytial pneumovirus; respiratory syncytial pneumovirus a; respiratory syncytial pneumovirus b; unindexed sequence; virus gene; genetic variability; genetics; molecular evolution; respiratory tract infection; Human respiratory syncytial virus; Hydrangea ringspot virus; Amino Acid Substitution; Epitopes; Evolution, Molecular; Genetic Variation; Genotype; GTP-Binding Proteins; Humans; Phylogeny; Respiratory Syncytial Viruses; Respiratory Tract Infections; Viral Proteins


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Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a flipflop phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Butantan Institute Virology Branch, Butantã, São Paulo

Department of Microbiology Institute of Biomedical Sciences University of São Paulo, São Paulo

Division of Medical Biology Adolfo Lutz Institute, São Paulo

Department of Cell Biology School of Medicine of Ribeirão Preto University of São Paulo, Ribeirão Preto, São Paulo

Pediatric Division University Hospital University of São Paulo, São Paulo

Division of Viral Diseases National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention, Atlanta, GA

STD/AIDS Reference and Training Centre, São Paulo, São Paulo

State University of São Paulo, São Paulo

Tropical Medicine Institute University of São Paulo, São Paulo

Department of Legal Medicine University of São Paulo Medical School, São Paulo

Center for Infectious Disease Dynamics Department of Biology Pennsylvania State University, University Park, PA

Fogarty International Center National Institutes of Health, Bethesda, MD

Document Type Journal article
Language English
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