Unveiling alternate pathways for SARS-CoV-2 infection via extracellular vesicle-mediated transfer of ACE2 and TMPRSS2
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Le résumé fourni par la source
The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the urgency of understanding viral entry mechanisms to develop effective therapeutic strategies. SARS-CoV-2 primarily exploits angiotensin-converting enzyme 2 (ACE2) as its entry receptor and relies on the serine protease TMPRSS2 to prime its spike protein, enabling membrane fusion and infection. Traditionally, TMPRSS2 has been described as a cell surface protein, but our study reveals that in human lung epithelial cells, TMPRSS2 is largely absent from the plasma membrane and instead resides intracellularly. We show that TMPRSS2 is secreted together with ACE2 in extracellular vesicles (EVs) from lung epithelial cells, which are subsequently taken up by non-epithelial cells, specifically alveolar macrophages, endothelial cells, and pericytes, that do not express TMPRSS2 or ACE2 mRNAs under homeostatic conditions. This EV uptake deposits ACE2 and TMPRSS2 protein onto recipient cells, equipping them for SARS-CoV-2 entry. By transferring these viral entry proteins, EVs expand the spectrum of susceptible cell types in the lung, offering a new explanation for how the virus can infect diverse cell populations and cause widespread tissue damage. Identifying EVs as vehicles for delivering functional ACE2 and TMPRSS2 across cell types reveals a previously unrecognized pathway of viral entry with important implications for not only COVID-19 pathogenesis but also for other viral infections that exploit similar entry mechanisms. These findings open new avenues for therapeutic intervention aimed at disrupting EV-mediated protein transfer, potentially limiting viral dissemination and severity, and may also represent a generalizable mechanism exploited by other viral pathogens, highlighting the potential relevance of EV-mediated protein transfer beyond SARS-CoV-2.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Unveiling alternate pathways for SARS-CoV-2 infection via extracellular vesicle-mediated transfer of ACE2 and TMPRSS2
- Date Crossref
- 10/04/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Icahn School of Medicine at Mount Sinai Department of Otolaryngology pays non établi dans la noticeUniversité ou école supérieure
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Cincinnati Children's Hospital Medical Center Center for Stem Cell and Organoid Medicine pays non établi dans la noticeÉtablissement de santé
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University of Cincinnati Medical Center Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Department of Otolaryngology — Icahn School of Medicine at Mount Sinai, Center for Stem Cell and Organoid Medicine — Cincinnati Children's Hospital Medical Center et Department of Pediatrics — University of Cincinnati Medical Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.