ArticlePloS one2017
A peptide-based approach to evaluate the adaptability of influenza A virus to humans based on its hemagglutinin proteolytic cleavage site.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- The Involvement of the Cryptococcal Yeast Kexin Protease in the Proteolytic Activation of the Uncleaved Influenza Virus Hemagglutinin Glycoprotein.MicrobiologyOpen · 2026Article
- Non-propagating RNA virus-vectored HA/NA vaccine prevents shedding of antigen-drifted H1N1 influenza virus in pigs.NPJ vaccines · 2026Article
- Phylogenetic and Molecular Characterization of a Novel Reassortant High-Pathogenicity Avian Influenza A (H7N6) Virus Detected in New Zealand Poultry.International journal of molecular sciences · 2025Article
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
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- The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins.Journal of virology · 2023Article
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- Function-based classification of hazardous biological sequences: Demonstration of a new paradigm for biohazard assessments.Frontiers in bioengineering and biotechnology · 2022Article
- Kallikreins emerge as new regulators of viral infections.Cellular and molecular life sciences : CMLS · 2021Review
- TMPRSS2 Activates Hemagglutinin-Esterase Glycoprotein of Influenza C Virus.Journal of virology · 2021Article
- Recent advances in rotavirus reverse genetics and its utilization in basic research and vaccine development.Archives of virology · 2021Review
- Host serine proteases TMPRSS2 and TMPRSS11D mediate proteolytic activation and trypsin-independent infection in group A rotaviruses.Journal of virology · 2021Article
- Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site.iScience · 2020Article
- Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site.SSRN · 2020Article
- SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.Virology · 2020Article
- Comparison of pathogenicity of subtype H9 avian influenza wild-type viruses from a wide geographic origin expressing mono-, di-, or tri-basic hemagglutinin cleavage sites.Veterinary research · 2020Article
- Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture.Influenza and other respiratory viruses · 2020Article
- Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.Frontiers in cellular neuroscience · 2020Article
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cleavage activation of the hemagglutinin (HA) protein by host proteases is a crucial step in the infection process of influenza A viruses (IAV). However, IAV exists in eighteen different HA subtypes in nature and their cleavage sites vary considerably. There is uncertainty regarding which specific proteases activate a given HA in the human respiratory tract. Understanding the relationship between different HA subtypes and human-specific proteases will be valuable in assessing the pandemic potential of circulating viruses. Here we utilized fluorogenic peptides mimicking the HA cleavage motif of representative IAV strains causing disease in humans or of zoonotic/pandemic potential and tested them with a range of proteases known to be present in the human respiratory tract. Our results show that peptides from the H1, H2 and H3 subtypes are cleaved efficiently by a wide range of proteases including trypsin, matriptase, human airway tryptase (HAT), kallikrein-related peptidases 5 (KLK5) and 12 (KLK12) and plasmin. Regarding IAVs currently of concern for human adaptation, cleavage site peptides from H10 viruses showed very limited cleavage by respiratory tract proteases. Peptide mimics from H6 viruses showed broader cleavage by respiratory tract proteases, while H5, H7 and H9 subtypes showed variable cleavage; particularly matriptase appeared to be a key protease capable of activating IAVs. We also tested HA substrate specificity of Factor Xa, a protease required for HA cleavage in chicken embryos and relevant for influenza virus production in eggs. Overall our data provide novel tool allowing the assessment of human adaptation of IAV HA subtypes.
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