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

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  • 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
  • Tanya Golubchik
  • Andrew J Pollard
  • RESCEU Investigators
  • Thea Kølsen Fischer (Member of study group)
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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.

Original languageEnglish
Article number5125
JournalNature Communications
Volume12
Issue number1
Pages (from-to)5125
DOIs
Publication statusPublished - 26 Aug 2021

ID: 67384531