دورية أكاديمية
Epithelial response to IFN‐γ promotes SARS‐CoV‐2 infection
| العنوان: | Epithelial response to IFN‐γ promotes SARS‐CoV‐2 infection |
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| المؤلفون: | Julian Heuberger, Jakob Trimpert, Daria Vladimirova, Christian Goosmann, Manqiang Lin, Rosa Schmuck, Hans‐Joachim Mollenkopf, Volker Brinkmann, Frank Tacke, Nikolaus Osterrieder, Michael Sigal |
| المصدر: | EMBO Molecular Medicine, Vol 13, Iss 4, Pp n/a-n/a (2021) |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | ACE2, differentiation, interferon, organoids, SARS‐CoV‐2, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract SARS‐CoV‐2, the agent that causes COVID‐19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin‐converting enzyme‐2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance, but severe cases of COVID‐19 are characterized by an inefficient immune response that fails to clear the infection. Using primary epithelial organoids from human colon, we explored how the central antiviral mediator IFN‐γ, which is elevated in COVID‐19, affects epithelial cell differentiation, ACE2 expression, and susceptibility to infection with SARS‐CoV‐2. In mouse and human colon, ACE2 is mainly expressed by surface enterocytes. Inducing enterocyte differentiation in organoid culture resulted in increased ACE2 production. IFN‐γ treatment promoted differentiation into mature KRT20+ enterocytes expressing high levels of ACE2, increased susceptibility to SARS‐CoV‐2 infection, and resulted in enhanced virus production in infected cells. Similarly, infection‐induced epithelial interferon signaling promoted enterocyte maturation and enhanced ACE2 expression. We here reveal a mechanism by which IFN‐γ‐driven inflammatory responses induce a vulnerable epithelial state with robust replication of SARS‐CoV‐2, which may have an impact on disease outcome and virus transmission. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202013191 |
| URL الوصول: | https://doaj.org/article/5396e49c30f44e5e8e0a119b1c47a08f |
| رقم الأكسشن: | edsdoj.5396e49c30f44e5e8e0a119b1c47a08f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202013191 |