ArticleJournal of virology2011
Residues of the human metapneumovirus fusion (F) protein critical for its strain-related fusion phenotype: implications for the virus replication cycle.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Genomic Surveillance of Human Metapneumovirus in the United States, 2010-2025.The Journal of infectious diseases · 2026Article
- A novel antiviral strategy targeting human metapneumovirus through pH modulation in human airway epithelial cells.The Journal of general virology · 2026Article
- Clinical Outcomes and Molecular Epidemiology of Human Metapneumovirus in Romanian Hospitalized Patients.Microorganisms · 2026Article
- Genomic surveillance of human metapneumovirus in the United States, 2010 - 2025.medRxiv : the preprint server for health sciences · 2026Article
- Human metapneumovirus: understanding the molecular mechanisms and pathology of infection.Journal of virology · 2025Review
- Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor.NPJ vaccines · 2025Article
- Human Metapneumovirus: A Comprehensive Epidemiological Analysis of a Global Respiratory Threat.Infection & chemotherapy · 2025Review
- Human metapneumovirus (hMPV) in 2025: emerging trends and insights from community and hospital-based respiratory panel analyses-a comprehensive review.Virology journal · 2025Review
- Structural basis for respiratory syncytial virus and human metapneumovirus neutralization.Current opinion in virology · 2023Review
- Respiratory Syncytial Virus and Human Metapneumovirus Infections in Three-Dimensional Human Airway Tissues Expose an Interesting Dichotomy in Viral Replication, Spread, and Inhibition by Neutralizing Antibodies.Journal of virology · 2020Article
- Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development.Vaccines · 2019Article
- Human metapneumovirus fusion protein triggering: Increasing complexities by analysis of new HMPV fusion proteins.Virology · 2019Article
- Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein.Nature communications · 2017Article
- Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation.PLoS pathogens · 2016Article
- DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans.Journal of virology · 2016Article
- Human Metapneumovirus Is Capable of Entering Cells by Fusion with Endosomal Membranes.PLoS pathogens · 2015Article
- Effect of in vitro syncytium formation on the severity of human metapneumovirus disease in a murine model.PloS one · 2015Article
- Roles of the putative integrin-binding motif of the human metapneumovirus fusion (f) protein in cell-cell fusion, viral infectivity, and pathogenesis.Journal of virology · 2014Article
- Article
- Breaking in: human metapneumovirus fusion and entry.Viruses · 2013Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The paramyxovirus F protein promotes fusion of the viral and cell membranes for virus entry, as well as cell-cell fusion for syncytium formation. Most paramyxovirus F proteins are triggered at neutral pH to initiate membrane fusion. Previous studies, however, demonstrated that human metapneumovirus (hMPV) F proteins are triggered at neutral or acidic pH in transfected cells, depending on the strain origin of the F sequences (S. Herfst et al., J. Virol. 82:8891-8895, 2008). We now report an extensive mutational analysis which identifies four variable residues (294, 296, 396, and 404) as the main determinants of the different syncytial phenotypes found among hMPV F proteins. These residues lie near two conserved histidines (H368 and H435) in a three-dimensional (3D) model of the pretriggered hMPV F trimer. Mutagenesis of H368 and H435 indicates that protonation of these histidines (particularly His435) is a key event to destabilize the hMPV F proteins that require low pH for cell-cell fusion. The syncytial phenotypes were reproduced in cells infected with the corresponding hMPV strains. However, the low-pH dependency for syncytium formation could not be related with a virus entry pathway dependent on an acidic environment. It is postulated that low pH may be acting for some hMPV strains as certain destabilizing mutations found in unusual strains of other paramyxoviruses. In any case, the results presented here and those reported by Schowalter et al. (J. Virol. 83:1511-1522, 2009) highlight the relevance of certain residues in the linker region and domain II of the pretriggered hMPV F protein for the process of membrane fusion.
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