SARS-CoV-2 productively infects human gut enterocytes

• Published in: Science (American Association for the Advancement of Science) Vol. 369; no. 6499; pp. 50 - 54
• Main Authors: Lamers, Mart M., Beumer, Joep, van der Vaart, Jelte, Knoops, Kèvin, Puschhof, Jens, Breugem, Tim I., Ravelli, Raimond B. G., Paul van Schayck, J., Mykytyn, Anna Z., Duimel, Hans Q., van Donselaar, Elly, Riesebosch, Samra, Kuijpers, Helma J. H., Schipper, Debby, van de Wetering, Willine J., de Graaf, Miranda, Koopmans, Marion, Cuppen, Edwin, Peters, Peter J., Haagmans, Bart L., Clevers, Hans
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 03.07.2020; American Association for the Advancement of Science
• Subjects: ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Betacoronavirus - physiology; Betacoronavirus - ultrastructure; Biology; Cell Biol; Cell Culture Techniques; Cell Differentiation; Cell Lineage; Cell Proliferation; Coronaviridae; Coronaviruses; COVID-19; Culture Media; Diarrhea; Digestive system; Disease transmission; Electron microscopy; Enterocytes; Enterocytes - metabolism; Enterocytes - ultrastructure; Enterocytes - virology; Epithelium; Gastrointestinal symptoms; Gastrointestinal tract; Gene Expression; Humans; Ileum - metabolism; Ileum - ultrastructure; Ileum - virology; Infectivity; Influenza; Intestine; Lung - virology; Male; Microbio; Organoids; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Receptors; Receptors, Virus - genetics; Receptors, Virus - metabolism; Respiratory diseases; Respiratory Mucosa - virology; RNA, Messenger - genetics; RNA, Messenger - metabolism; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome-related coronavirus - physiology; Viral diseases; Virus Replication; Viruses; Vomiting
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abc1669

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an influenza-like disease with a respiratory transmission route; however, patients often present with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, and cells in the inner-gut lining express the receptor that SARS-CoV-2 uses to gain entry to cells. Lamers et al. used human intestinal organoids, a “mini-gut” cultured in a dish, to demonstrate that SARS-CoV-2 readily replicates in an abundant cell type in the gut lining—the enterocyte—resulting in the production of large amounts of infective virus particles in the intestine. This work demonstrates that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut. Science , this issue p. 50 SARS-CoV-2 infects enterocytes in human small intestinal organoids. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2, as demonstrated by confocal and electron microscopy. Enterocytes produced infectious viral particles, whereas messenger RNA expression analysis of hSIOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology.