SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression
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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 BartfeldAbstract
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.
Journal details
Journal
Stem Cell Reports
Volume
19
Issue number
5
Pages
629-638
Available online
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Publisher website (DOI)
10.1016/j.stemcr.2024.03.008
Europe PubMed Central
38670110
Pubmed
38670110
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