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Open Access Research

Genetic diversity and evolution of human metapneumovirus fusion protein over twenty years

Chin-Fen Yang4, Chiaoyin K Wang4, Sharon J Tollefson1, Rohith Piyaratna1, Linda D Lintao4, Marla Chu4, Alexis Liem4, Mary Mark4, Richard R Spaete4, James E Crowe123 and John V Williams123*

Author Affiliations

1 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA

2 Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN, USA

3 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

4 MedImmune Vaccines, Inc, Mountain View, CA, USA

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Virology Journal 2009, 6:138  doi:10.1186/1743-422X-6-138

Published: 9 September 2009



Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in children. We examined the diversity and molecular evolution of HMPV using 85 full-length F (fusion) gene sequences collected over a 20-year period.


The F gene sequences fell into two major groups, each with two subgroups, which exhibited a mean of 96% identity by predicted amino acid sequences. Amino acid identity within and between subgroups was higher than nucleotide identity, suggesting structural or functional constraints on F protein diversity. There was minimal progressive drift over time, and the genetic lineages were stable over the 20-year period. Several canonical amino acid differences discriminated between major subgroups, and polymorphic variations tended to cluster in discrete regions. The estimated rate of mutation was 7.12 × 10-4 substitutions/site/year and the estimated time to most recent common HMPV ancestor was 97 years (95% likelihood range 66-194 years). Analysis suggested that HMPV diverged from avian metapneumovirus type C (AMPV-C) 269 years ago (95% likelihood range 106-382 years).


HMPV F protein remains conserved over decades. HMPV appears to have diverged from AMPV-C fairly recently.