title: Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene.
abstract: Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012-2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.|Bioinformatics Group, J. Craig Venter Institute, Rockville, MD, USA.|Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Schobel
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Karla M
authors.initials: KM
authors.lastname: Stucker
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Anderson
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.|Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Shankar
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Jayati
authors.initials: J
authors.lastname: Bera
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Vinita
authors.initials: V
authors.lastname: Puri
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Meghan H
authors.initials: MH
authors.lastname: Shilts
authors.affiliation: Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Rosas-Salazar
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Halpin
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Fedorova
authors.affiliation: Bioinformatics Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Shrivastava
authors.affiliation: Bioinformatics Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Stockwell
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.|Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.|Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Tina V
authors.initials: TV
authors.lastname: Hartert
authors.affiliation: Infectious Diseases Group, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Suman R
authors.initials: SR
authors.lastname: Das
mesh_terms: D001499:Bayes Theorem; D019143:Evolution, Molecular; D005260:Female; D020440:Gene Duplication; D016679:Genome, Viral; D006031:Glycosylation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics*; D017423:Sequence Analysis, RNA; D013714:Tennessee / Q000453:epidemiology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D014759:Viral Envelope Proteins; C116204:attachment protein G