Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

PLoS Pathogens

Osvaldo A. Sant'Anna¹  Viviane F. Botosso¹  Eddie C. Holmes²  Eurico Arruda³  Eduardo Massad⁴  Mirthes Ueda⁵  Edison L. Durigon⁶  Teresa C. T. Peret⁷  and the VGDN Consortium⁸  Paolo M. de A. Zanotto⁹  Klaus E. Stewien⁹  Alfredo E. Gilio^1,10  Sandra E. Vieira^1,10  Leda F. Jamal^1,11  Maria I. de M. C. Pardini^1,12  João R. R. Pinho^1,13 

[1] Butantan Institute, Virology Branch, Butantã, São Paulo, Brazil;Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, Pennsylvania, United States of America;Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;Department of Legal Medicine, University of São Paulo Medical School, São Paulo, Brazil;Division of Medical Biology, Adolfo Lutz Institute, São Paulo, Brazil;Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America;Gastroenteritis and Respiratory Viruses Laboratory Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America;Laboratory of Clinical Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;Pediatric Division, University Hospital of the University of São Paulo, São Paulo, Brazil;STD/AIDS Reference and Training Centre, São Paulo, São Paulo, Brazil;State University of São Paulo, São Paulo, Brazil;Tropical Medicine Institute, University of São Paulo, São Paulo, Brazil

关键词: Brazil;    Viral evolution;    Evolutionary immunology;    Nucleotide sequencing;    Phylogenetic analysis;    Sequence alignment;    Phylogenetics;    Polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.1000254

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY