Genome-Wide Analyses of Human Respiratory Syncytial Viruses Provide Insights into Evolutionary Dynamics

Human Respiratory syncytial virus (HRSV) is a leading cause of acute lower respiratory tract infections. It is essential to monitor its genomic characteristics. In this study, we analyzed the variation and evolutionary features of HRSV A and HRSV B using whole-genome data, with a focus on their evolutionary features post-COVID-19. Our findings revealed: (i) the mutation rates of HRSV A genes were generally higher than those of HRSV B genes, with the primary mutation directions for both subtypes being C to T, T to C, G to A, and A to G; (ii) multiple lineages of both subtypes that were prevalent during the pandemic are no longer circulating, likely related to the founder effect caused by non-pharmaceutical interventions; (iii) the lineage-defining amino acids on the neutralizing antigens F and G of the circulating lineages post SARS-CoV-2 pandemic exhibited significant temporal specificity; (iv) HRSV B predominated over A in 2023, and the lineage-defining amino acids of the HRSV B F protein located on or very close to major neutralizing antigenic sites, and several lineage-defining amino acids of the G protein were under strong positive selection. These observations suggested that the HRSV B showed stronger adaptive evolutionary features compared to HRSV A post-pandemic. Combining with the fact that several lineage-defining amino acids are located in the replication-related proteins, we hypothesized a potential model of synergistic evolution mediated by multi-protein mutations in the adaptive evolution of circulating strains. However, the impact of these amino acid changes on the viral properties requires further experimental validation.