title: Local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing.
abstract: Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.
  
  
  OBJECTIVE
  The new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Agoti
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: James R
authors.initials: JR
authors.lastname: Otieno
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Munywoki
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Mwihuri
authors.affiliation: Public Health England, Salisbury, United Kingdom.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya University of Warwick, School of Life Sciences and WIDER, Warwick, United Kingdom.
authors.forename: D James
authors.initials: DJ
authors.lastname: Nokes
authors.affiliation: The Wellcome Trust Sanger Institute, Cambridge, United Kingdom Division of Infection Immunity, University College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.affiliation: The Wellcome Trust Sanger Institute, Cambridge, United Kingdom mc13@sanger.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cotten
mesh_terms: D002675:Child, Preschool; D016000:Cluster Analysis; D019143:Evolution, Molecular; D016679:Genome, Viral; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006780:Hospitals, Rural; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya; D008969:Molecular Sequence Data; D058974:Phylogeography; D018357:Respiratory Syncytial Virus Infections / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017385:Sequence Homology