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Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Functional implications of respiratory syncytial virus F sequence variability: a comparative analysis using
Kim Stobbelaar1,2,3, Lotte Jacobs1, Francisco I Serrano-Cano1
1Laboratory of Microbiology, Parasitology and Hygiene, Faculty of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Respiratory syncytial virus (RSV) fusion (F) protein sequence variation is limited but shows phenotypic differences between RSV-A and RSV-B strains. Continued surveillance of RSV F sequences and antibody sensitivity is crucial for effective prophylactics.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Respiratory syncytial virus (RSV) is a significant global health concern, particularly for young children.
- Limited therapeutic options exist, but new prophylactics targeting the RSV fusion (F) glycoprotein have been licensed.
- Understanding F protein variability and its phenotypic impact is crucial for vaccine and prophylactic efficacy.
Purpose of the Study:
- To analyze the genomic and phenotypic variability of contemporary RSV isolates.
- To investigate how F protein sequence variations influence viral characteristics and susceptibility to monoclonal antibodies (mAbs).
- To assess the importance of ongoing RSV surveillance for prophylactic development.
Main Methods:
- Analysis of full F gene sequences from 105 contemporary RSV isolates from children with lower respiratory tract infections.
- Functional characterization of 20 selected isolates based on F antigenic site variation.
- Comparison of RSV-A and RSV-B strain characteristics, including syncytium formation and thermal stability.
Main Results:
- RSV-A strains exhibited higher genetic diversity than RSV-B strains.
- Sequence variability in mAb-binding sites did not fully explain differential mAb neutralization sensitivity.
- RSV-A strains showed larger syncytium size and lower syncytium frequency compared to RSV-B strains.
- Some RSV-A isolates demonstrated enhanced stability at higher temperatures.
Conclusions:
- Genomic and phenotypic variability in contemporary RSV isolates is generally limited but shows notable exceptions.
- Phenotypic differences between RSV subgroups highlight the need for clinical isolate-based evaluations.
- Continuous RSV surveillance, including sequencing and antibody sensitivity testing, is essential to monitor for and counter potential escape mutants and ensure prophylactic effectiveness.
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