# Molecular Evolution of the Fusion (F) Genes in Human Metapneumovirus Genotype B

## TL;DR

This study examines the molecular evolution of the F gene in HMPV-B, finding it evolves slowly with stable antigenic features, which could aid in developing antibody-based treatments.

## Contribution

The study provides new insights into the evolutionary constraints and antigenic stability of the HMPV-B F gene using a large sequence dataset.

## Key findings

- The HMPV-B F gene diverged into sublineages B1 and B2 around 1937.
- The F gene evolves at a rate of 1.01 × 10−3 substitutions/site/year under strong purifying selection.
- Neutralizing antibody binding regions in the F protein show high conservation despite limited amino acid variation.

## 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.