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SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression.
- Source :
-
Stem cell reports [Stem Cell Reports] 2024 May 14; Vol. 19 (5), pp. 629-638. Date of Electronic Publication: 2024 Apr 25. - Publication Year :
- 2024
-
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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Viral Tropism
Organoids virology
Organoids metabolism
Epithelial Cells metabolism
Epithelial Cells virology
Virus Replication
Animals
Angiotensin-Converting Enzyme 2 metabolism
Angiotensin-Converting Enzyme 2 genetics
SARS-CoV-2 physiology
COVID-19 virology
COVID-19 metabolism
Intestinal Mucosa metabolism
Intestinal Mucosa virology
Gastric Mucosa metabolism
Gastric Mucosa virology
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 38670110
- Full Text :
- https://doi.org/10.1016/j.stemcr.2024.03.008