Distinct patterns of within-host virus populations 2 between two subgroups of human respiratory syncytial 3 virus

Gu-Lung Lin, Simon B Drysdale, Matthew D Snape, Daniel P 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 Martinon-Torres, Harish Nair, Rory Bowden, Tanya Golubchik, Andrew J Pollard

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalNature Communications
DOIs
Publication statusPublished - 26 Aug 2021

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