Molecular Evolution of the Fusion (F) Genes in Human Parainfluenza Virus Type 2

Human parainfluenza virus type 2 (HPIV2) is a clinically significant respiratory pathogen, which highlights the necessity of studies on its molecular evolution. This study investigated the evolutionary dynamics, phylodynamics, and structural characteristics of the HPIV2 fusion (F) gene using a comprehensive dataset spanning multiple decades and geographic regions. Phylogenetic analyses revealed two distinct clusters of HPIV2 F gene sequences, which were estimated to have diverged from a common ancestor approximately a century ago. Cluster 1 demonstrated a higher evolutionary rate and genetic diversity compared to the more stable cluster 2. Bayesian Skyline Plot analyses indicated a significant increase in the effective population size of the F gene between 2005 and 2015; potentially linked to enhanced diagnostic and surveillance capabilities. Structural modeling identified conserved conformational epitopes predominantly in the apex and stalk regions of the F protein. These findings underscore the evolutionary constraints and antigenic landscape of the HPIV2 F protein.