Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene

Schobel, Seth A.; Stucker, Karla M.; Moore, Martin L.; Anderson, Larry J.; Larkin, Emma K.; Shankar, Jyoti; Bera, Jayati; Puri, Vinita; Shilts, Meghan H.; Rosas-Salazar, Christian; Halpin, Rebecca A.; Fedorova, Nadia; Shrivastava, Susmita; Stockwell, Timothy B.; Peebles, R. Stokes; Hartert, Tina V.; Das, Suman R.

Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.