Toward unified molecular surveillance of RSV: A proposal for genotype definition

Stephanie Goya*, Mónica Galiano, Inne Nauwelaers, Alfonsina Trento, Peter J. Openshaw, Alicia S. Mistchenko, Maria Zambon, Mariana Viegas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: Human respiratory syncytial virus (RSV) is classified into antigenic subgroups A and B. Thirteen genotypes have been defined for RSV-A and 20 for RSV-B, without any consensus on genotype definition. Methods: We evaluated clustering of RSV sequences published in GenBank until February 2018 to define genotypes by using maximum likelihood and Bayesian phylogenetic analyses and average p-distances. Results: We compared the patterns of sequence clustering of complete genomes; the three surface glycoproteins genes (SH, G, and F, single and concatenated); the ectodomain and the 2nd hypervariable region of G gene. Although complete genome analysis achieved the best resolution, the F, G, and G-ectodomain phylogenies showed similar topologies with statistical support comparable to complete genome. Based on the widespread geographic representation and large number of available G-ectodomain sequences, this region was chosen as the minimum region suitable for RSV genotyping. A genotype was defined as a monophyletic cluster of sequences with high statistical support (≥80% bootstrap and ≥0.8 posterior probability), with an intragenotype p-distance ≤0.03 for both subgroups and an intergenotype p-distance ≥0.09 for RSV-A and ≥0.05 for RSV-B. In this work, the number of genotypes was reduced from 13 to three for RSV-A (GA1-GA3) and from 20 to seven for RSV-B (GB1-GB7). Within these, two additional levels of classification were defined: subgenotypes and lineages. Signature amino acid substitutions to complement this classification were also identified. Conclusions: We propose an objective protocol for RSV genotyping suitable for adoption as an international standard to support the global expansion of RSV molecular surveillance.

Original languageEnglish
Pages (from-to)274-285
Number of pages12
JournalInfluenza and other Respiratory Viruses
Volume14
Issue number3
DOIs
Publication statusPublished - 1 May 2020

Bibliographical note

Funding Information:
This research did not receive specific funding from agencies in the public, commercial, or not‐for‐profit sectors. Consejo Nacional de Investigaciones Científicas y Técnicas supported SG and MV. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires supported ASM. IN, MG, PO and MZ are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections and the Biomedical Research Centre (BRC) at Imperial College Healthcare NHS Trust, funded by NIHR in partnership with PHE. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Funding Information:
This research did not receive specific funding from agencies in the public, commercial, or not-for-profit sectors. Consejo Nacional de Investigaciones Cient?ficas y T?cnicas supported SG and MV. Comisi?n de Investigaciones Cient?ficas de la Provincia de Buenos Aires supported ASM. IN, MG, PO and MZ are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections and the Biomedical Research Centre (BRC) at Imperial College Healthcare NHS Trust, funded by NIHR in partnership with PHE. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We would like to thank Burcu Ermetal for assistance with the use of the treesub program and interpretation of data.

Publisher Copyright:
© 2020 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd

Keywords

  • average genetic distance
  • genotypes
  • global molecular surveillance
  • human orthopneumovirus
  • human respiratory syncytial virus
  • lineages
  • phylogenetic analysis
  • subgenotypes

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