tetano
Editor, Senior Moderator
J Med Virol
. 2024 Jul;96(7):e29783.
doi: 10.1002/jmv.29783. Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model
Meta Volcic[SUP] 1 [/SUP], Rayhane Nchioua[SUP] 1 [/SUP], Chiara Pastorio[SUP] 1 [/SUP], Fabian Zech[SUP] 1 [/SUP], Isabell Haußmann[SUP] 2 [/SUP], Daniel Sauter[SUP] 2 [/SUP], Clarissa Read[SUP] 3 [/SUP], Paul Walther[SUP] 3 [/SUP], Frank Kirchhoff[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Omicron; SARS‐CoV‐2; gut barrier; intestinal epithelium model; tight junctions.
. 2024 Jul;96(7):e29783.
doi: 10.1002/jmv.29783. Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model
Meta Volcic[SUP] 1 [/SUP], Rayhane Nchioua[SUP] 1 [/SUP], Chiara Pastorio[SUP] 1 [/SUP], Fabian Zech[SUP] 1 [/SUP], Isabell Haußmann[SUP] 2 [/SUP], Daniel Sauter[SUP] 2 [/SUP], Clarissa Read[SUP] 3 [/SUP], Paul Walther[SUP] 3 [/SUP], Frank Kirchhoff[SUP] 1 [/SUP]
Affiliations
- PMID: 38965890
- DOI: 10.1002/jmv.29783
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.
Keywords: Omicron; SARS‐CoV‐2; gut barrier; intestinal epithelium model; tight junctions.