Molecular evolutionary dynamics of respiratory syncytial virus group A in recurrent epidemics in coastal Kenya.


Otieno, JR; Agoti, CN; Gitahi, CW; Bett, A; Ngama, M; Medley, GF; Cane, PA; Nokes, DJ; (2016) Molecular evolutionary dynamics of respiratory syncytial virus group A in recurrent epidemics in coastal Kenya. Journal of virology. ISSN 0022-538X DOI: 10.1128/JVI.03105-15

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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 efficiency of pre-existing immune responses. We analyzed the molecular evolutionary changes in the attachment (G) glycoprotein of RSV-A viruses collected over 13 epidemic seasons (2000 - 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, 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 dataset was estimated at 3.58 x 10(-3) [95% HPD: 3.04 - 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 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 both in local and global settings. On longer time scales (∼7 years) there is sequential replacement of genotypes, while 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.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Global Health and Development
Research Centre: Social and Mathematical Epidemiology (SaME)
SaME Modelling & Economics
PubMed ID: 26937038
Web of Science ID: 375126100013
URI: http://researchonline.lshtm.ac.uk/id/eprint/2534267

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