Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus
Lin G-L., Drysdale SB., Snape MD., O’Connor D., Brown A., MacIntyre-Cockett G., Mellado-Gomez E., de Cesare M., Bonsall D., Ansari MA., Öner D., Aerssens J., Butler C., Bont L., Openshaw P., Martinón-Torres F., Nair H., Bowden R., Campbell H., Cunningham S., Bogaert D., Beutels P., Wildenbeest J., Clutterbuck E., McGinley J., Thwaites R., Wiseman D., Gómez-Carballa A., Rodriguez-Tenreiro C., Rivero-Calle I., Dacosta-Urbieta A., Heikkinen T., Meijer A., Fischer TK., van den Berge M., Giaquinto C., Abram M., Dormitzer P., Stoszek S., Gallichan S., Rosen B., Molero E., Machin N., Spadetto M., Golubchik T., Pollard AJ.
AbstractHuman 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.