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.

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Publication Details

Journal
medRxiv
Published
2026-01-21
DOI
https://doi.org/10.64898/2026.01.18.26344359
Primary Topic
Respiratory viral infections research
Type
article
Field-Weighted Citation Impact
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article

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

Laurence W. Busse, Cristie Columbus, Nathan Ivan Shapiro, JS Steingrub et al.
medRxiv
Respiratory viral infections research
article

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

Laurence W. Busse, Cristie Columbus, Nathan Ivan Shapiro, JS Steingrub, Adam S. Lauring, Ryan E. Malosh, Truscon Rachel, Abhijit Duggal, Fatimah S. Dawood, Akram Khan, Matthew Exline, Diya Surie, Nida Qadir, David Hager, Jennie H. Kwon, Nicholas J Johnson, Yuwei Zhu, William J. Fitzsimmons, Ithan D. Peltan, Adit A Ginde, Ivana A. Vaughn, Basmah Safdar, Amira Mohamed, Jarrod M. Mosier, Matthew E Prekker, Kevin Ma, Estelle S. Harris, Wesley H. Self, Emily E. Bendall, Arnold Monto, James D. Chappell, Jennifer G. Wilson, Natasha Halasa
article en

Abstract

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.

medRxiv
Albert Einstein College of Medicine (US), Cleveland Clinic (US), Montefiore Medical Center (US), Baystate Medical Center (US), University of Arizona (US), Johns Hopkins University (US), Emory University (US), Henry Ford Health System (US), University of California, Los Angeles (US), Oregon Health & Science University (US), National Center for Immunization and Respiratory Diseases (US), University of Washington (US), University of Utah (US), University of Michigan (US), Johns Hopkins Medicine (US), Hadassah Medical Center (IL), Hennepin County Medical Center (US), Intermountain Medical Center (US), Yale University (US), Baylor Scott & White Medical Center - Temple (US), Baylor Scott & White Health (US), Wake Forest University (US), The Ohio State University (US), Vanderbilt University Medical Center (US), University of Colorado Denver (US), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 79%
Respiratory viral infections research
DOISourceOpenAlex
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