التفاصيل البيبلوغرافية
العنوان: |
Attenuated replication and damaging effects of SARS‐CoV‐2 Omicron variants in an intestinal epithelial barrier model. |
المؤلفون: |
Volcic, Meta, Nchioua, Rayhane, Pastorio, Chiara, Zech, Fabian, Haußmann, Isabell, Sauter, Daniel, Read, Clarissa, Walther, Paul, Kirchhoff, Frank |
المصدر: |
Journal of Medical Virology; Jul2024, Vol. 96 Issue 7, p1-13, 13p |
مصطلحات موضوعية: |
SARS-CoV-2 Omicron variant, SARS-CoV-2, SARS-CoV-2 Delta variant, INTESTINAL barrier function, COVID-19 |
مستخلص: |
Many COVID‐19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function is thought to play a key role in Long COVID. Despite its importance, the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco‐2 cells, mucus‐secreting HT29 cells and Raji cells. This gut epithelial model allows efficient differentiation of Caco‐2 cells into microfold‐like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS‐CoV‐2 infection. Early strains of SARS‐CoV‐2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin‐1, occludin, and ZO‐1. In comparison, Omicron subvariants also depleted ZO‐1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir, the fusion inhibitor EK1 and the transmembrane serine protease 2 inhibitor Camostat inhibited SARS‐CoV‐2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS‐CoV‐2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |