Genomic characterization of respiratory syncytial virus genotypes circulating in the paediatric population of Sydney, NSW, Australia

Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing significant morbidity and mortality. We used pathogen genomics to characterize the population structure and genetic signatures of RSV isolates circulating in children in New South Wales between 2016 and 2018 and to understand the evolutionary dynamics of these strains in the context of publicly available RSV genomes from the region and globally. Whole-genome phylogenetic analysis demonstrated the co-circulation of a few major RSV clades in the paediatric population from Sydney. The whole-genome- based genotypes A23 (RSV -A ON1- like genotype) and B6 (RSV -B BA9- like genotype) were the predominant RSV -A and RSV -B genotypes circulating during the study period, respectively. These genotypes were characterized with high levels of diversity of predicted N-and O-linked glycosylation patterns in both the G and F glycoproteins. Interestingly, a novel 72-nucleotide triplication in the sequence that corresponds to the C-terminal region of the G gene was identified in four of the A23 genotype sequenced in this study. Consistently, the population dynamics analysis demonstrated a continuous increase in the effective population size of A23 and B6 genotypes globally. Further investigations including functional mapping of mutations and identifying the impact of sequence changes on virus fitness are highly required. This study highlights the potential impact of an integrated approach that uses WG- based phylogeny and studying selective pressure events in understanding the emergence and dissemination of RSV genotypes.