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SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression

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journal contribution
posted on 2024-05-01, 10:20 authored by Mindaugas Paužuolis, Diana Fatykhova, Boris Zühlke, Torsten Schwecke, Mastura Neyazi, Pilar Samperio-Ventayol, Carmen Aguilar, Nicolas Schlegel, Simon Dökel, Markus Ralser, Andreas Hocke, Christine Krempl, Sina Bartfeld
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.


Crick (Grant ID: 10134, Grant title: Ralser FC001134)