ArticleJournal of virology2013
Matriptase, HAT, and TMPRSS2 activate the hemagglutinin of H9N2 influenza A viruses.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 137 citations in OpenAlex.
- 3-Amidinophenylalanine-Derived Inhibitors' Antiviral Effect Against H1N1 Influenza A Virus.Antibiotics (Basel, Switzerland) · 2026Article
- Structural basis of TMPRSS11D specificity and autocleavage activation.Nature communications · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Identification of the critical residues of TMPRSS2 for entry and host range of human coronavirus HKU1.Journal of virology · 2024Article
- Molecular characterisation of novel reassortants of the G57 genotype of low-pathogenic avian influenza H9N2 virus isolated from poultry farms in Malaysia.Archives of virology · 2024Article
- PK/PD investigation of antiviral host matriptase/TMPRSS2 inhibitors in cell models.Scientific reports · 2024Article
- Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19.Journal of virology · 2024Article
- Establishment of reverse genetics for genotype VII Newcastle disease virus and altering the cell tropism by inserting TMPRSS2 into the viral genome.Virus genes · 2023Article
- In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes.Biomedicines · 2023Article
- The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation.Current opinion in virology · 2023Review
- Genetic, Antigenic, and Pathobiological Characterization of H9 and H6 Low Pathogenicity Avian Influenza Viruses Isolated in Vietnam from 2014 to 2018.Microorganisms · 2023Article
- Roles of host proteases in the entry of SARS-CoV-2.Animal diseases · 2023Review
- Protective Efficacy of Inactivated H9N2 Vaccine in Turkey Poults under Both Experimental and Field Conditions.Vaccines · 2022Article
- Hemagglutinin Subtype Specificity and Mechanisms of Highly Pathogenic Avian Influenza Virus Genesis.Viruses · 2022Review
- The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China.Viruses · 2022Article
- The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment.International journal of molecular sciences · 2022Review
- SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.EMBO molecular medicine · 2022Article
- Proteolytic activation of SARS-CoV-2 spike protein.Microbiology and immunology · 2022Review
- Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect.Journal of enzyme inhibition and medicinal chemistry · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza A viruses of the subtype H9N2 circulate worldwide and have become highly prevalent in poultry in many countries. Moreover, they are occasionally transmitted to humans, raising concern about their pandemic potential. Influenza virus infectivity requires cleavage of the surface glycoprotein hemagglutinin (HA) at a distinct cleavage site by host cell proteases. H9N2 viruses vary remarkably in the amino acid sequence at the cleavage site, and many isolates from Asia and the Middle East possess the multibasic motifs R-S-S-R and R-S-R-R, but are not activated by furin. Here, we investigated proteolytic activation of the early H9N2 isolate A/turkey/Wisconsin/1/66 (H9-Wisc) and two recent Asian isolates, A/quail/Shantou/782/00 (H9-782) and A/quail/Shantou/2061/00 (H9-2061), containing mono-, di-, and tribasic HA cleavage sites, respectively. All H9N2 isolates were activated by human proteases TMPRSS2 (transmembrane protease, serine S1 member 2) and HAT (human airway trypsin-like protease). Interestingly, H9-782 and H9-2061 were also activated by matriptase, a protease widely expressed in most epithelia with high expression levels in the kidney. Nephrotropism of H9N2 viruses has been observed in chickens, and here we found that H9-782 and H9-2061 were proteolytically activated in canine kidney (MDCK-II) and chicken embryo kidney (CEK) cells, whereas H9-Wisc was not. Virus activation was inhibited by peptide-mimetic inhibitors of matriptase, strongly suggesting that matriptase is responsible for HA cleavage in these kidney cells. Our data demonstrate that H9N2 viruses with R-S-S-R or R-S-R-R cleavage sites are activated by matriptase in addition to HAT and TMPRSS2 and, therefore, can be activated in a wide range of tissues what may affect virus spread, tissue tropism and pathogenicity.
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