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

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. Here, we report an expanded genomic surveillance of HMPV in the United States, utilizing 325 newly sequenced samples from two cohorts: the household-based HIVE study (2010-2022) in Michigan and the multicenter IVY network (2022-2025) of hospitalized adults. Our analyses revealed the continued predominance of the A2.2.2 clade and little geographic structure in the US. Genomic diversity is 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 shows limited antigenic variation and low rates of nonsynonymous substitutions, suggesting stability in epitopes targeted by vaccine candidates. These findings underscore the utility of enhanced genomic surveillance for understanding HMPV evolution and informing vaccine development.