SARS-CoV-2 productively infects human gut enterocytes
Mart M. Lamers1,*, Joep Beumer2,*, Jelte van der Vaart2,*, Kèvin Knoops3, Jens Puschhof2, Tim I. Breugem1, Raimond B. G. Ravelli3, J. Paul van Schayck3, Anna Z. Mykytyn1, Hans Q. Duimel3, Elly van Donselaar3, Samra Riesebosch1, Helma J. H. Kuijpers3, Debby Schippers1, Willine J. van de Wetering3, Miranda de Graaf1, Marion Koopmans1, Edwin Cuppen4,5, Peter J. Peters3, Bart L. Haagmans1,†, Hans Clevers2,†,‡
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Science 01 May 2020:
eabc1669
DOI: 10.1126/science.abc1669
Abstract
The virus 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 via 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. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology
