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

• DOI: 10.1038/s41467-021-25265-4
• Publication Date: 2021-08-26T10:05:29Z
• Authors: Gu-Lung Lin; Simon B. Drysdale; Matthew D. Snape; Daniel O’Connor; Anthony Brown; George MacIntyre-...; Esther Mellado-Gomez; Mariateresa de Ce...; David Bonsall; M. Azim Ansari; Deniz Öner; Jeroen Aerssens; Christopher Butler; Louis Bont; Peter Openshaw; Federico Martinón...; Harish Nair; Rory Bowden; ; Harry Campbell; Steve Cunningham; Debby Bogaert; Philippe Beutels; Joanne Wildenbeest; Elizabeth Clutter...; Joseph McGinley; Ryan Thwaites; Dexter Wiseman; Alberto Gómez-Car...; Carmen Rodriguez-...; Irene Rivero-Calle; Ana Dacosta-Urbieta; Terho Heikkinen; Adam Meijer; Thea Kølsen Fischer; Maarten van den B...; Carlo Giaquinto; Michael Abram; Philip Dormitzer; Sonia Stoszek; Scott Gallichan; Brian Rosen; Eva Molero; Nuria Machin; Martina Spadetto; Tanya Golubchik; Andrew J. Pollard
• Keywords: Male; Science; DIVERSITY; Mutation, Missense; 610; PROTEIN; PALIVIZUMAB; Respiratory Syncytial Virus Infections; Virus Replication; Article; Viral Proteins; 03 medical and health sciences; 616; INFECTION; Humans; Aged; 0303 health sciences; Science & Technology; Q; Aged; Antigenic Variation; Female; Genetic Variation; Humans; Infant; Male; Mutation, Missense; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Proteins; Virus Replication; RSV; Genetic Variation; Infant; PREVENTION; Antigenic Variation; EVOLUTION; 3. Good health; Multidisciplinary Sciences; ALIGNMENT; Respiratory Syncytial Virus, Human; Mutation; ANTIBODIES; Science & Technology - Other Topics; RESCEU Investigators; Female; Respiratory Syncytial Virus; Missense; RESISTANCE; Human

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.