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Published on: April 4, 2019
Molecular Evolution of the Fusion (F) Genes in Human Metapneumovirus Genotype B
Tatsuya Shirai1,2,3, Fuminori Mizukoshi4, Mitsuru Sada2
1Department of Respiratory Viruses, National Institute of Infectious Diseases, Japan Institute for Health Security, Musashimurayama-shi 208-0011, Tokyo, Japan.
Abstract:
Human metapneumovirus genotype B (HMPV-B) is an important respiratory pathogen, requiring detailed elucidation of the evolutionary and antigenic features of its fusion (F) gene. Using 500 sequences collected between 1982 and 2024, we investigated the molecular evolution, phylodynamics, and structural epitope landscape of the HMPV-B F gene. Time-scaled phylogeny dated the divergence of sublineages B1 and B2 to around 1937, and Bayesian Skyline Plot analysis showed that these sublineages exhibited distinct demographic trajectories over time. The F gene evolved at a rate of 1.01 × 10-3 substitutions/site/year; however, amino acid variation remained limited, consistent with pervasive purifying selection, with 39% of codons under strong negative selection and little consensus evidence for positive selection. Conformational B-cell epitope prediction demonstrated a high degree of conservation across neutralizing antibody binding regions (sites Ø and I-V), and amino acid substitutions occurring within these sites were not predicted to substantially alter epitope architecture. Together, these findings indicate that the HMPV-B F gene evolves under strong evolutionary constraint while maintaining stable antigenic features, supporting the potential for antibody-based strategies that target neutralizing antibody binding regions of the F protein.
Insights
Human metapneumovirus genotype B (HMPV-B) fusion (F) gene shows limited variation and stable antigenic features. This suggests antibody-based strategies targeting conserved regions of the F protein are promising for HMPV-B.
Area of Science:
- Virology
- Molecular Evolution
- Immunology
Background:
- Human metapneumovirus genotype B (HMPV-B) is a significant respiratory pathogen.
- Understanding the evolutionary and antigenic characteristics of its fusion (F) gene is crucial.
Purpose of the Study:
- To investigate the molecular evolution, phylodynamics, and epitope landscape of the HMPV-B F gene.
- To assess the potential for antibody-based therapeutic strategies.
Main Methods:
- Analysis of 500 HMPV-B F gene sequences (1982-2024).
- Time-scaled phylogeny and Bayesian Skyline Plot analysis.
- Epitope prediction for conformational B-cell binding sites.
Main Results:
- HMPV-B sublineages B1 and B2 diverged around 1937 with distinct demographic histories.
- The F gene evolves at 1.01 × 10⁻³ substitutions/site/year, with limited amino acid variation due to strong purifying selection.
- Neutralizing antibody binding regions (sites Ø and I-V) are highly conserved, with substitutions unlikely to alter epitope structure.
Conclusions:
- The HMPV-B F gene evolves under significant constraint, maintaining stable antigenic properties.
- Conserved neutralizing antibody binding regions suggest potential for effective antibody-based interventions against HMPV-B.
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