Characterizing the Genomic Diversity, Evolution and Phylogeography of Respiratory Syncytial Virus Genotype ON1 in Kenya

Abstract

Background: In December 2010, a new genotype of respiratory syncytial virus (RSV) with a 72-nucleotide duplication within the attachment (G) gene was identified in Ontario, Canada, and named ON1. Using the ON1 as a unique tag, this study aimed to understand; (1) how new RSV variants are introduced, spread and persist in communities, (2) the genomic signatures that define the emergent RSV variants and whether such substitutions may be associated with potential fitness advantages, and (3) the patterns of RSV spread across geographically defined regions (local and global). Methods: Partial G gene (n=483) and whole genome (n=184) sequence datasets collected between 2010 and 2016 were analyzed using genetic diversity, phylogenetics and statistical methods to understand the molecular epidemiology of RSV in Kilifi County, Coastal Kenya. Further, Kenyan (partial G gene; n=2526) and global (full G gene, n=2238; whole genome, n=1194) sequence datasets collected between 1977 to 2016 were analysed in a Bayesian framework for the inference of the phylogeographic history of local and global RSV spread, respectively. Results: Following initial detection of the genotype ON1 in Kilifi in 2012, there was rapid replacement of the previously circulating RSV group A genotype GA2 by ON1 in subsequent epidemics. While this suggests elevated fitness of ON1 viruses, there was no clear evidence of altered pathogenicity of ON1 relative to GA2 in Kilifi. Signature amino acid substitutions were identified between surface proteins (G, F), polymerase (L) and matrix M2-1 proteins of Kilifi ON1 and GA2 viruses, suggesting co-evolution amongst antigenic and non-antigenic genes of RSV variants. Genetic and phylogenetic analyses reaffirmed previous conclusions that each RSV epidemic is characterized by the frequent introduction of multiple variants, few of which persist across epidemics. Finally, the phylogeographic analyses predicted the northern hemisphere to be the major source population of RSV into the tropics and the southern hemisphere and virus spread between locations in close proximity to be important for virus persistence within a country. Conclusions: Tracking the ON1 tag offered important insights into RSV evolution and transmission. The use of whole genome sequencing and surveying all the variation throughout the genome will be crucial for greater understanding, and potentially improved control, of this important pathogen. However, there is a need for a more targeted approach to RSV surveillance and sequencing that will help build a better picture of RSV spread at different scales.