02581nas a2200637   4500000000100000000000100001008004100002260001500043653003600058653002000094653002800114653002500142653001700167653002300184653001800207653001600225653002000241653001100261653001000272653000900282653000900291653001400300653002700314653001900341653002100360653002300381653001500404653005800419653002200477100001900499700001600518700002400534700001800558700001800576700001900594700002600613700002400639700002000663700001900683700002300702700002100725700002500746700001900771700003100790700002100821700002000842700001700862700002000879700002100899700001700920245005800937300001000995490000801005520091601013022001401929       2020                            d  c2020-07-0310aAngiotensin-Converting Enzyme 210aBetacoronavirus10aCell Culture Techniques10aCell Differentiation10aCell Lineage10aCell Proliferation10aCulture Media10aenterocytes10aGene expression10aHumans10aIleum10aLung10aMale10aorganoids10aPeptidyl-Dipeptidase A10aRNA, Messenger10aReceptors, Virus10aRespiratory Mucosa10aSARS-CoV-210aSevere acute respiratory syndrome-related coronavirus10aVirus Replication1 aMart M. Lamers1 aJoep Beumer1 aJelte van der Vaart1 aKèvin Knoops1 aJens Puschhof1 aTim I. Breugem1 aRaimond B. G. Ravelli1 aJ. Paul van Schayck1 aAnna Z. Mykytyn1 aHans Q. Duimel1 aElly van Donselaar1 aSamra Riesebosch1 aHelma J. H. Kuijpers1 aDebby Schipper1 aWilline J. van de Wetering1 aMiranda de Graaf1 aMarion Koopmans1 aEdwin Cuppen1 aPeter J. Peters1 aBart L. Haagmans1 aHans Clevers00aSARS-CoV-2 productively infects human gut enterocytes  a50-540 v3693 aSevere 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.  a1095-9203