| Title: |
Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model |
| Authors: |
Volčič, Meta; Nchioua, Rayhane; Pastorio, Chiara; Zech, Fabian; Haußmann, Isabell; Sauter, Daniel; Read, Clarissa; Walther, Paul; Kirchhoff, Frank |
| Publisher Information: |
Universität Ulm |
| Publication Year: |
2024 |
| Collection: |
OPARU (OPen Access Repository of Ulm University) |
| Subject Terms: |
Gut barrier; Intestinal epithelium model; Omicron; SARS-CoV-2; Tight junctions |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| DOI: |
10.18725/OPARU-58543 |
| Availability: |
https://doi.org/10.18725/OPARU-58543; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-58618-6 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.2ACE3792 |
| Database: |
BASE |