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SARS-CoV-2 productively infects human gut enterocytes

Mart M. Lamers, Joep Beumer, Jelte van der Vaart, Kèvin Knoops, Jens Puschhof, Tim I. Breugem, Raimond B. G. Ravelli, J. Paul van Schayck, Anna Z. Mykytyn, Hans Q. Duimel, Elly van Donselaar, Samra Riesebosch, Helma J. H. Kuijpers, Debby Schipper, Willine J. van de Wetering, Miranda de Graaf, Marion Koopmans, Edwin Cuppen, Peter J. Peters, Bart L. Haagmans, Hans Clevers

Published: 03/07/2020

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.

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