SARS-CoV-2 productively infects human gut enterocytes

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.; Schippers, Debby; van de Wetering, Willine J.; de Graaf, Miranda; Koopmans, Marion; Cuppen, Edwin; Peters, Peter J.; Haagmans, Bart L.; Clevers, Hans

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