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 Cesare, David Bonsall, M. Azim Ansari, Deniz Öner, Jeroen Aerssens, Christopher Butler, Louis Bont, Peter Openshaw, Federico Martinón-Torres, Harish Nair, Rory Bowden, Tanya Golubchik and Andrew J. Pollard
Additional contact information
Gu-Lung Lin: University of Oxford
Simon B. Drysdale: University of Oxford
Matthew D. Snape: University of Oxford
Daniel O’Connor: University of Oxford
Anthony Brown: University of Oxford
George MacIntyre-Cockett: University of Oxford
Esther Mellado-Gomez: University of Oxford
Mariateresa Cesare: University of Oxford
David Bonsall: University of Oxford
M. Azim Ansari: University of Oxford
Deniz Öner: Janssen Pharmaceutica NV
Jeroen Aerssens: Janssen Pharmaceutica NV
Christopher Butler: University of Oxford
Louis Bont: University Medical Center Utrecht
Peter Openshaw: Imperial College London
Federico Martinón-Torres: Hospital Clínico Universitario de Santiago de Compostela
Harish Nair: University of Edinburgh
Rory Bowden: University of Oxford
Tanya Golubchik: University of Oxford
Andrew J. Pollard: University of Oxford

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25265-4

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