SARS-CoV-2 productively infects human gut enterocytes

Publication date

2020-07-03

Authors

Lamers, Mart M
Beumer, Joep
van der Vaart, Jelte Y.ORCID 0000-0002-4126-8420
Knoops, Kèvin
Puschhof, Jens
Breugem, Tim I
Ravelli, Raimond B G
Paul van Schayck, J
Mykytyn, Anna Z
Duimel, Hans Q

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Article

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Abstract

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.

Keywords

Betacoronavirus/physiology, Cell Culture Techniques, Cell Differentiation, Cell Lineage, Cell Proliferation, Culture Media, Enterocytes/metabolism, Gene Expression, Humans, Ileum/metabolism, Lung/virology, Male, Organoids, Peptidyl-Dipeptidase A/genetics, RNA, Messenger/genetics, Receptors, Virus/genetics, Respiratory Mucosa/virology, SARS Virus/physiology, Virus Replication, General, Journal Article, Research Support, Non-U.S. Gov't

Citation

Lamers, M M, Beumer, J, van der Vaart, J, Knoops, K, Puschhof, J, Breugem, T I, Ravelli, R B G, Paul van Schayck, J, Mykytyn, A Z, Duimel, H Q, van Donselaar, E, Riesebosch, S, Kuijpers, H J H, Schippers, D, van de Wetering, W J, de Graaf, M, Koopmans, M, Cuppen, E, Peters, P J, Haagmans, B L & Clevers, H 2020, 'SARS-CoV-2 productively infects human gut enterocytes', Science, vol. 369, no. 6499, pp. 50-54. https://doi.org/10.1126/science.abc1669