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

Nat Commun. 2021 Aug 26;12(1):5125. doi: 10.1038/s41467-021-25265-4.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigenic Variation
  • Female
  • Genetic Variation
  • Humans
  • Infant
  • Male
  • Mutation, Missense
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Virus, Human / classification
  • Respiratory Syncytial Virus, Human / genetics*
  • Respiratory Syncytial Virus, Human / immunology
  • Respiratory Syncytial Virus, Human / physiology
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Virus Replication

Substances

  • Viral Proteins