tetano
Editor, Senior Moderator
Stem Cell Reports
. 2024 Apr 21:S2213-6711(24)00083-3.
doi: 10.1016/j.stemcr.2024.03.008. Online ahead of print. SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression
Mindaugas Paužuolis[SUP] 1 [/SUP], Diana Fatykhova[SUP] 2 [/SUP], Boris Zühlke[SUP] 3 [/SUP], Torsten Schwecke[SUP] 4 [/SUP], Mastura Neyazi[SUP] 1 [/SUP], Pilar Samperio-Ventayol[SUP] 5 [/SUP], Carmen Aguilar[SUP] 1 [/SUP], Nicolas Schlegel[SUP] 6 [/SUP], Simon Dökel[SUP] 7 [/SUP], Markus Ralser[SUP] 8 [/SUP], Andreas Hocke[SUP] 3 [/SUP], Christine Krempl[SUP] 9 [/SUP], Sina Bartfeld[SUP] 10 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal (GI) symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium are sparse and a side-by-side comparison of the infection in the major segments of the GI tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to angiotensin-converting enzyme 2 (ACE2) as a critical factor, and, indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in GI biopsies of patients mirrors SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach, is likely to be important in viral replication and possibly transmission.
Keywords: ACE2; SARS-CoV-2; gastrointestinal epithelium; infection model; intestine; organoids; stomach.
. 2024 Apr 21:S2213-6711(24)00083-3.
doi: 10.1016/j.stemcr.2024.03.008. Online ahead of print. SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression
Mindaugas Paužuolis[SUP] 1 [/SUP], Diana Fatykhova[SUP] 2 [/SUP], Boris Zühlke[SUP] 3 [/SUP], Torsten Schwecke[SUP] 4 [/SUP], Mastura Neyazi[SUP] 1 [/SUP], Pilar Samperio-Ventayol[SUP] 5 [/SUP], Carmen Aguilar[SUP] 1 [/SUP], Nicolas Schlegel[SUP] 6 [/SUP], Simon Dökel[SUP] 7 [/SUP], Markus Ralser[SUP] 8 [/SUP], Andreas Hocke[SUP] 3 [/SUP], Christine Krempl[SUP] 9 [/SUP], Sina Bartfeld[SUP] 10 [/SUP]
Affiliations
- PMID: 38670110
- DOI: 10.1016/j.stemcr.2024.03.008
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal (GI) symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium are sparse and a side-by-side comparison of the infection in the major segments of the GI tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to angiotensin-converting enzyme 2 (ACE2) as a critical factor, and, indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in GI biopsies of patients mirrors SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach, is likely to be important in viral replication and possibly transmission.
Keywords: ACE2; SARS-CoV-2; gastrointestinal epithelium; infection model; intestine; organoids; stomach.