Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
Gu-Lung Lin, Simon B. Drysdale, Matthew D. Snape, Daniel O’Connor, Anthony Brown, George MacIntyre-Cockett, Esther Mellado-Gomez, Mariateresa de Cesare, David Bonsall, M. Azim Ansari, Deniz Öner, Jeroen Aerssens, Christopher Butler, Louis Bont, Peter Openshaw, Federico Martinón‐Torres, Harish Nair, Rory Bowden, RESCEU Investigators, Harry Campbell, Steve Cunningham, Debby Bogaert, Philippe Beutels, Joanne Wildenbeest, Elizabeth Clutterbuck, Joseph McGinley, Ryan S. Thwaites, Dexter Wiseman, Alberto Gómez‐Carballa, Carmen Rodrı́guez-Tenreiro, Irene Rivero‐Calle, Ana Dacosta-Urbieta, Terho Heikkinen, Adam Meijer, Thea Kølsen Fischer, Maarten van den Berge, Carlo Giaquinto, Michael E. Abram, Philip R. Dormitzer, Sonia Stoszek, Scott Gallichan, Brian Rosen, Eva Molero, Núria Machín, Martina Spadetto, Tanya Golubchik, Andrew J. Pollard
Abstract
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.