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 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

Journal: Nature communications 2021;12(1):5125

PMID: 34446722

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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.

Address: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. [email protected].; NIHR Oxford Biomedical Research Centre, Oxford, UK. [email protected].; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St George's, University of London, London, UK.; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Translational Biomarkers, Infectious Diseases Therapeutic Area, Janssen Pharmaceutica NV, Beerse, Belgium.; Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.; Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.; ReSViNET Foundation, Zeist, Netherlands.; National Heart and Lung Institute, Imperial College London, London, UK.; Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.; Genetics, Vaccines, Infectious Diseases, and Pediatrics Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.; Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Division of Advanced Technology and Biology, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

DOI: 10.1038/s41467-021-25265-4

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MeSH Terms: Aged, Antigenic Variation, Female, Genetic Variation, Humans, Infant, Male, Mutation, Missense, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Viral Proteins, Virus Replication