Phylodynamics of human metapneumovirus and evidence for a duplication-deletion model in G gene variant evolution

Background

In December 2024, human metapneumovirus (hMPV) gained global attention amid rising cases in Chinese hospitals, prompting a World Health, Organization (WHO) statement indicating case numbers remained within expected ranges. To assess whether a variant of public health concern was emerging and to examine global hMPV phylodynamics, we conducted a genomic surveillance study in western Washington State.

Study design

We sequenced hMPV genomes from inpatient and outpatient samples collected between 2021 and 2025 in western Washington State and constructed phylogenomic and phylodynamic trees.

Results

We obtained 60 hMPV-A and 39 hMPV-B genomes, including 13 from November 2024 to January 2025. Following COVID-19 pandemic disruptions, hMPV seasonality returned to typical patterns after 2023. Genomic analysis showed hMPV-A predominance since 2022–23, with co-circulation of A2b1, A2b2, B1, and B2 sublineages. The A2b2 sublineage was most prevalent and all genomes carried a 111-nt G gene duplication. Phylogenetic evidence suggests the 111-nt variant evolved from a prior 180-nt duplication via a 69-nt deletion rather than through independent duplication events. Most sublineages showed multiple co-circulating clades, except A2b1. Phylodynamics showed recovery of global diversity after pandemic-related declines and a higher evolutionary rate in hMPV-A compared to hMPV-B. No distinct evolutionary features of heightened concern were detected.

Conclusions

Despite recent concerns, our findings indicate that hMPV circulation in, the USA follows expected seasonal patterns, with ongoing introductions of diverse viral variants from preexisting sublineages rather than emergence of a novel variant. Continued genomic surveillance is essential, particularly as vaccine development progresses.