ArticleJournal of virology2014
DESC1 and MSPL activate influenza A viruses and emerging coronaviruses for host cell entry.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 91 citations in OpenAlex.
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- The impact of TMPRSS11A rs353163 and rs977728 polymorphisms on COVID-19 severity: genotypic and clinical associations.Molecular biology reports · 2025Article
- Cathepsin L and transmembrane serine protease 11E mediate trypsin-independent entry of porcine deltacoronavirus into Huh7 cells.Journal of virology · 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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- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.bioRxiv : the preprint server for biology · 2024Article
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Aprotinin-Drug against Respiratory Diseases.International journal of molecular sciences · 2023Review
- Identification of Embryonic Chicken Proteases Activating Newcastle Disease Virus and Their Roles in the Pathogenicity of Virus Used asJournal of virology · 2023Article
- In vivo secondary structural analysis of Influenza A virus genomic RNA.Cellular and molecular life sciences : CMLS · 2023Article
- TMPRSS11E-dward Scissorhands? Proteolysis Potentiates Lung Inflammation during Pathogen Insult.American journal of respiratory cell and molecular biology · 2023Article
- Broad antiviral and anti-inflammatory efficacy of nafamostat against SARS-CoV-2 and seasonal coronaviruses in primary human bronchiolar epithelia.Nano select : open access · 2022Article
- IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike.Frontiers in immunology · 2022Article
- Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.Scientific reports · 2021Article
- Quantifying the effect of trypsin and elastase on in vitro SARS-CoV infections.Virus research · 2021Article
- Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.Life science alliance · 2021Article
- Host serine proteases TMPRSS2 and TMPRSS11D mediate proteolytic activation and trypsin-independent infection in group A rotaviruses.Journal of virology · 2021Article
- The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the influenza virus and coronavirus surface proteins. Expression of TMPRSS2 is essential for the spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analyzed TTSPs, reported to be expressed in the respiratory system, for the ability to activate influenza viruses and coronaviruses. We found that MSPL and, to a lesser degree, DESC1 are expressed in human lung tissue and cleave and activate the spike proteins of the Middle East respiratory syndrome and severe acute respiratory syndrome coronaviruses for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases that could promote the amplification of influenza viruses and emerging coronaviruses in humans and might constitute targets for antiviral intervention. Importance: Activation of influenza viruses by host cell proteases is essential for viral infectivity and the enzymes responsible are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1.
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