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

• Published in: PLoS pathogens 2009-01, Vol.5 (1), p.e1000254-e1000254
• Main Authors: Botosso, Viviane F, Zanotto, Paolo M de A, Ueda, Mirthes, Arruda, Eurico, Gilio, Alfredo E, Vieira, Sandra E, Stewien, Klaus E, Peret, Teresa C T, Jamal, Leda F, Pardini, Maria I de M C, Pinho, João R R, Massad, Eduardo, Sant'anna, Osvaldo A, Holmes, Eddie C, Durigon, Edison L
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Amino acids; Binding sites; Epitopes; Evolution; Evolution & development; Evolution, Molecular; Evolutionary Biology/Evolutionary and Comparative Genetics; Evolutionary Biology/Microbial Evolution and Genomics; G proteins; Genes; Genetic aspects; Genetic diversity; Genetic Variation; Genotype; GTP-Binding Proteins - genetics; Human respiratory syncytial virus; Humans; Phylogenetics; Phylogeny; Physiological aspects; Population; Proteins; Respiratory syncytial virus; Respiratory Syncytial Viruses - genetics; Respiratory Tract Infections; Viral Proteins - genetics; Virology/Immune Evasion; Virology/Virus Evolution and Symbiosis
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000254

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 "flip-flop" 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.