ArticleEMBO molecular medicine2022
SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Early cell-autonomous and niche-mediated epithelial response to influenza infection in primary alveolar organoids.JCI insight · 2026Article
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- Associations of 6600 SomaScan proteins with demographic, lifestyle, environmental and health characteristics in Chinese adults.Scientific reports · 2026Article
- Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis.Viruses · 2026Review
- Associations of 2923 Olink proteins with demographic, lifestyle, environmental and health characteristics in middle-aged Chinese adults.European journal of epidemiology · 2025Article
- Ciliated cells promote high infectious potential of influenza A virus through the efficient intracellular activation of hemagglutinin.Journal of virology · 2025Article
- Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Acute Impact of Nonoptimal Ambient Temperatures on Plasma Levels of 3000 Proteins in Chinese Adults.Environmental science & technology · 2025Article
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.Nature communications · 2024Article
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- Pigs lackingFrontiers in genome editing · 2023Article
- Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids.Signal transduction and targeted therapy · 2022Article
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- A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant.Cell discovery · 2022Article
- SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.EMBO molecular medicine · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SPINK6 was identified in human skin as a cellular inhibitor of serine proteases of the KLK family. Airway serine proteases are required to cleave hemagglutinin (HA) of influenza A viruses (IAVs) to initiate an infection in the human airway. We hypothesized that SPINK6 may inhibit common airway serine proteases and restrict IAV activation. We demonstrate that SPINK6 specifically suppresses the proteolytic activity of HAT and KLK5, HAT- and KLK5-mediated HA cleavage, and restricts virus maturation and replication. SPINK6 constrains the activation of progeny virions and impairs viral growth; and vice versa, blocking endogenous SPINK6 enhances HA cleavage and viral growth in physiological-relevant human airway organoids where SPINK6 is intrinsically expressed. In IAV-infected mice, SPINK6 significantly suppresses viral growth and improves mouse survival. Notably, individuals carrying the higher SPINK6 expression allele were protected from human H7N9 infection. Collectively, SPINK6 is a novel host inhibitor of serine proteases in the human airway and restricts IAV activation.
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