Functional implications of respiratory syncytial virus F sequence variability: a comparative analysis using contemporary RSV isolates DOI Creative Commons
Kim Stobbelaar, Lotte Jacobs,

Francisco I. Serrano-Cano

et al.

mSphere, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

ABSTRACT Respiratory syncytial virus (RSV) remains a major global health issue. Therapeutic options are limited, but new prophylactics, all targeting the fusion (F) glycoprotein, were recently licensed. Although F sequence variation is it unclear if and how this variability translates to phenotypical differences. We analyzed full sequences of 105 contemporary RSV isolates, gathered from children presenting with acute lower respiratory tract infections. Based on antigenic site variation, 20 isolates selected for functional characterization. diversity generally low, overall mean pairwise distance between RSV-A strains higher than RSV-B (0.014 vs 0.008, P < 0.001). Sequence in known monoclonal antibody (mAb)-binding sites seems insufficient explain divergent often subgroup-dependent sensitivity mAb neutralization. Despite comparable growth rates, syncytium size was (mean 61.68 [SD 24.51] 31.72 11.64], 0.001), frequency 25.37 9.20] 47.85 [11.52], 0.001) strains. For temperatures associated increased inactivation, although some displayed manifestly stability. Genomic phenotypic among our noticeable exceptions. The availability prophylactics corroborates importance continued surveillance identify changes sequence, including mutations that reduce efficacy or lead escape mutants. Surveillance should include both sequencing data an evaluation prophylactic antibodies, using clinical isolates. IMPORTANCE cause infections young worldwide. Recent progress has led ways prevent serious RSV-associated disease. virus’s protein key focus vaccine development because helps enter host cells well conserved across different However, small differences could affect behaves vitro . In study, we, therefore, samples under two who presented (12 8 RSV-B) testing, based their sequences. Phenotypic reference strains, such as stability at 4°C susceptibility neutralization, highlight viruses isolated recent samples. significant observed traits related protein, subgroups within, underlying molecular mechanisms remain unclear. Ongoing monitoring critical ensure current future vaccines effective.

Language: Английский

Functional implications of respiratory syncytial virus F sequence variability: a comparative analysis using contemporary RSV isolates DOI Creative Commons
Kim Stobbelaar, Lotte Jacobs,

Francisco I. Serrano-Cano

et al.

mSphere, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

ABSTRACT Respiratory syncytial virus (RSV) remains a major global health issue. Therapeutic options are limited, but new prophylactics, all targeting the fusion (F) glycoprotein, were recently licensed. Although F sequence variation is it unclear if and how this variability translates to phenotypical differences. We analyzed full sequences of 105 contemporary RSV isolates, gathered from children presenting with acute lower respiratory tract infections. Based on antigenic site variation, 20 isolates selected for functional characterization. diversity generally low, overall mean pairwise distance between RSV-A strains higher than RSV-B (0.014 vs 0.008, P < 0.001). Sequence in known monoclonal antibody (mAb)-binding sites seems insufficient explain divergent often subgroup-dependent sensitivity mAb neutralization. Despite comparable growth rates, syncytium size was (mean 61.68 [SD 24.51] 31.72 11.64], 0.001), frequency 25.37 9.20] 47.85 [11.52], 0.001) strains. For temperatures associated increased inactivation, although some displayed manifestly stability. Genomic phenotypic among our noticeable exceptions. The availability prophylactics corroborates importance continued surveillance identify changes sequence, including mutations that reduce efficacy or lead escape mutants. Surveillance should include both sequencing data an evaluation prophylactic antibodies, using clinical isolates. IMPORTANCE cause infections young worldwide. Recent progress has led ways prevent serious RSV-associated disease. virus’s protein key focus vaccine development because helps enter host cells well conserved across different However, small differences could affect behaves vitro . In study, we, therefore, samples under two who presented (12 8 RSV-B) testing, based their sequences. Phenotypic reference strains, such as stability at 4°C susceptibility neutralization, highlight viruses isolated recent samples. significant observed traits related protein, subgroups within, underlying molecular mechanisms remain unclear. Ongoing monitoring critical ensure current future vaccines effective.

Language: Английский

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