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

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

doi:10.1016/j.stemcr.2024.03.008

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

Stem Cell Reports. 2024 Apr 21:S2213-6711(24)00083-3. doi: 10.1016/j.stemcr.2024.03.008. Online ahead of print.

Authors

Affiliations

¹ Research Centre for Infectious Diseases, Institute for Molecular Infection Biology, Julius Maximilians Universität Würzburg, Würzburg, Germany.
² Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁴ Core Facility for High-Throughput Mass Spectrometry, Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁵ Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Medical Biotechnology, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
⁶ Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
⁷ Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
⁸ Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany; The Francis Crick Institute, Molecular Biology of Metabolism Laboratory, London, UK; The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹ Institute for Virology and Immunobiology, Julius Maximilian University of Würzburg, Würzburg, Germany.
¹⁰ Research Centre for Infectious Diseases, Institute for Molecular Infection Biology, Julius Maximilians Universität Würzburg, Würzburg, Germany; Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Medical Biotechnology, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany. Electronic address: s.bartfeld@tu-berlin.de.

PMID: 38670110
DOI: 10.1016/j.stemcr.2024.03.008

Abstract

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.