Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus

Author:

Lin Gu-LungORCID,Drysdale Simon B.ORCID,Snape Matthew D.,O’Connor DanielORCID,Brown AnthonyORCID,MacIntyre-Cockett George,Mellado-Gomez Esther,de Cesare MariateresaORCID,Bonsall David,Ansari M. Azim,Öner Deniz,Aerssens Jeroen,Butler Christopher,Bont Louis,Openshaw PeterORCID,Martinón-Torres FedericoORCID,Nair HarishORCID,Bowden RoryORCID,Campbell Harry,Cunningham Steve,Bogaert Debby,Beutels Philippe,Wildenbeest Joanne,Clutterbuck Elizabeth,McGinley Joseph,Thwaites Ryan,Wiseman Dexter,Gómez-Carballa Alberto,Rodriguez-Tenreiro Carmen,Rivero-Calle Irene,Dacosta-Urbieta Ana,Heikkinen Terho,Meijer Adam,Fischer Thea Kølsen,van den Berge Maarten,Giaquinto Carlo,Abram Michael,Dormitzer Philip,Stoszek Sonia,Gallichan Scott,Rosen Brian,Molero Eva,Machin Nuria,Spadetto Martina,Golubchik TanyaORCID,Pollard Andrew J.ORCID,

Abstract

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.

Funder

Innovative Medicines Initiative

EC | Horizon 2020 Framework Programme

European Federation of Pharmaceutical Industries and Associations

NIHR Oxford Biomedical Research Centre NIHR Thames Valley and South Midlands Clinical Research Network British Research Council REspiratory Syncytial virus Consortium in EUrope

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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