ArticleJournal of virology2021
Hemagglutinins of Avian Influenza Viruses Are Proteolytically Activated by TMPRSS2 in Human and Murine Airway Cells.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.Emerging microbes & infections · 2026Article
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- Host Cell Virus Interactions: Molecular Mechanisms, Immune Modulation, Viral Pathogenesis, and Emerging Therapeutic Targets.Viruses · 2026Review
- Structural determinants of rotavirus proteolytic activation.PLoS pathogens · 2025Article
- Genetic resilience or resistance in poultry against avian influenza virus: mirage or reality?Journal of virology · 2025Review
- Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum Efficacy against Corona and Influenza Viruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- H5N1 Avian Influenza: A Narrative Review of Scientific Advances and Global Policy Challenges.Viruses · 2025Review
- Long-term culture of chicken tracheal organoids for the purpose of avian influenza virus research.Virology journal · 2025Article
- Human Transmembrane Serine Protease 2 (TMPRSS2) on Human Seminal Fluid Extracellular Vesicles Is Proteolytically Active.Journal of extracellular vesicles · 2025Article
- Review
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Article
- Avian influenza in birds: Insights from a comprehensive review.Veterinary world · 2024Review
- Novel proteolytic activation of Ebolavirus glycoprotein GP by TMPRSS2 and cathepsin L at an uncharted position can compensate for furin cleavage.Virus research · 2024Article
- PK/PD investigation of antiviral host matriptase/TMPRSS2 inhibitors in cell models.Scientific reports · 2024Article
- ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.Journal of virology · 2024Article
- Article
- Article
- Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host.Viruses · 2023Review
- Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.Life science alliance · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Cleavage of the influenza A virus (IAV) hemagglutinin (HA) by host proteases is indispensable for virus replication. Most IAVs possess a monobasic HA cleavage site cleaved by trypsin-like proteases. Previously, the transmembrane protease TMPRSS2 was shown to be essential for proteolytic activation of IAV HA subtypes H1, H2, H7, and H10 in mice. In contrast, additional proteases are involved in activation of certain H3 IAVs, indicating that HAs with monobasic cleavage sites can differ in their sensitivity to host proteases. Here, we investigated the role of TMPRSS2 in proteolytic activation of avian HA subtypes H1 to H11 and H14 to H16 in human and mouse airway cell cultures. Using reassortant viruses carrying representative HAs, we analyzed HA cleavage and multicycle replication in (i) lung cells of TMPRSS2-deficient mice and (ii) Calu-3 cells and primary human bronchial cells subjected to morpholino oligomer-mediated knockdown of TMPRSS2 activity. TMPRSS2 was found to be crucial for activation of H1 to H11, H14, and H15 in airway cells of human and mouse. Only H9 with an R-S-S-R cleavage site and H16 were proteolytically activated in the absence of TMPRSS2 activity, albeit with reduced efficiency. Moreover, a TMPRSS2-orthologous protease from duck supported activation of H1 to H11, H15, and H16 in MDCK cells. Together, our data demonstrate that in human and murine respiratory cells, TMPRSS2 is the major activating protease of almost all IAV HA subtypes with monobasic cleavage sites. Furthermore, our results suggest that TMPRSS2 supports activation of IAV with a monobasic cleavage site in ducks.
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Registered trials
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