دورية أكاديمية
Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate
العنوان: | Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate |
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المؤلفون: | Endika Prieto-Fernández, Leire Egia-Mendikute, Laura Vila-Vecilla, Alexandre Bosch, Adrián Barreira-Manrique, So Young Lee, Ana García-del Río, Asier Antoñana-Vildosola, Borja Jiménez-Lasheras, Leire Moreno-Cugnon, Jesús Jiménez-Barbero, Edurne Berra, June Ereño-Orbea, Asis Palazon |
المصدر: | Emerging Microbes and Infections, Vol 10, Iss 1, Pp 1065-1076 (2021) |
بيانات النشر: | Taylor & Francis Group, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Infectious and parasitic diseases LCC:Microbiology |
مصطلحات موضوعية: | SARS-CoV-2, hypoxia, ACE2, heparan sulfate, syndecan-1, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502 |
الوصف: | A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1α-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 22221751 2222-1751 |
Relation: | https://doaj.org/toc/2222-1751 |
DOI: | 10.1080/22221751.2021.1932607 |
URL الوصول: | https://doaj.org/article/af10c8771b7745ab83dcafd99d208588 |
رقم الأكسشن: | edsdoj.f10c8771b7745ab83dcafd99d208588 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 22221751 |
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DOI: | 10.1080/22221751.2021.1932607 |