title: Molecular Evolutionary Dynamics of Respiratory Syncytial Virus Group A in Recurrent Epidemics in Coastal Kenya.
abstract: The characteristic recurrent epidemics of human respiratory syncytial virus (RSV) within communities may result from the genetic variability of the virus and associated evolutionary adaptation, reducing the efficiency of preexisting immune responses. We analyzed the molecular evolutionary changes in the attachment (G) glycoprotein of RSV-A viruses collected over 13 epidemic seasons (2000 to 2012) in Kilifi (n = 649), Kenya, and contemporaneous sequences (n = 1,131) collected elsewhere within Kenya and 28 other countries. Genetic diversity in the G gene in Kilifi was dynamic both within and between epidemics, characterized by frequent new variant introductions and limited variant persistence between consecutive epidemics. Four RSV-A genotypes were detected in Kilifi: ON1 (11.9%), GA2 (75.5%), GA5 (12.3%), and GA3 (0.3%), with predominant genotype replacement of GA5 by GA2 and then GA2 by ON1. Within these genotypes, there was considerable variation in potential N-glycosylation sites, with GA2 and ON1 viruses showing up to 15 different patterns involving eight possible sites. Further, we identified 15 positively selected and 34 genotype-distinguishing codon sites, with six of these sites exhibiting both characteristics. The mean substitution rate of the G ectodomain for the Kilifi data set was estimated at 3.58 × 10(-3) (95% highest posterior density interval = 3.04 to 4.16) nucleotide substitutions/site/year. Kilifi viruses were interspersed in the global phylogenetic tree, clustering mostly with Kenyan and European sequences. Our findings highlight ongoing genetic evolution and high diversity of circulating RSV-A strains, locally and globally, with potential antigenic differences. Taken together, these provide a possible explanation on the nature of recurrent local RSV epidemics.
  
  
  
  The mechanisms underlying recurrent epidemics of RSV are poorly understood. We observe high genetic diversity in circulating strains within and between epidemics in both local and global settings. On longer time scales (∼7 years) there is sequential replacement of genotypes, whereas on shorter time scales (one epidemic to the next or within epidemics) there is a high turnover of variants within genotypes. Further, this genetic diversity is predicted to be associated with variation in antigenic profiles. These observations provide an explanation for recurrent RSV epidemics and have potential implications on the long-term effectiveness of vaccines.
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya jotieno@kemri-wellcome.org.
authors.forename: James R
authors.identifier: http://orcid.org/0000-0001-9790-2307
authors.initials: JR
authors.lastname: Otieno
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.|Department of Biomedical Sciences, Pwani University, Kilifi, Kenya.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Agoti
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Gitahi
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Ann
authors.initials: A
authors.lastname: Bett
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
authors.forename: Mwanajuma
authors.initials: M
authors.lastname: Ngama
authors.affiliation: Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Graham F
authors.initials: GF
authors.lastname: Medley
authors.affiliation: Public Health England, Salisbury, United Kingdom.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
authors.affiliation: Epidemiology and Demography Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.|School of Life Sciences and WIDER, University of Warwick, Coventry, United Kingdom.
authors.forename: D James
authors.initials: DJ
authors.lastname: Nokes
mesh_terms: D016000:Cluster Analysis; D058872:Epidemics; D019143:Evolution, Molecular; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D056004:Molecular Dynamics Simulation; D010802:Phylogeny; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics*