Genomic surveillance of human metapneumovirus in the United States, 2010–2025

BACKGROUND: Human metapneumovirus (HMPV) is a significant cause of acute respiratory illness in both children and adults, yet its genomic epidemiology remains understudied compared to other respiratory viruses. METHODS: Hybrid capture and whole genome sequencing were performed on 616 HMPV positive specimens from two cohorts: the household-based HIVE study (2010-2022) in Michigan and the multicenter IVY network (2022-2025) of hospitalized adults. Consensus sequences were generated using IRMA, clades were annotated using Nextclade, and phylogenetic trees were constructed separately for HMPV-A and HMPV-B using IQTree and TreeTime. Analysis of selection by dN/dS was performed using SLAC. RESULTS: We obtained complete genomes from 325 specimens. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the US. Genomic diversity was highest in the glycoprotein (G); we identified a shift from variants bearing the 180nt duplication to ones with a 111nt duplication. Phylogenetic analyses supported the duplication-deletion model for the origin of the duplications. The conserved fusion (F) protein showed limited antigenic variation and low rates of nonsynonymous substitutions. CONCLUSIONS: These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development. There was little genomic diversity in epitopes targeted by vaccine candidates.