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

doi:10.1126/science.abc1669

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 Schippers, Willine J van de Wetering, Miranda de Graaf, Marion Koopmans, Edwin Cuppen, Peter J Peters, Bart L HaagmansHans Clevers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (hSlOs), 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 hSlOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSlOs serve as an experimental model for coronavirus infection and biology.

Original language	English
Pages (from-to)	50-54
Number of pages	5
Journal	Science
Volume	369
Issue number	6499
Early online date	1 May 2020
DOIs	https://doi.org/10.1126/science.abc1669
Publication status	Published - 3 Jul 2020

Keywords

CORONAVIRUS
REPLICATION
EXPRESSION
ENTEROIDS
NETWORK
ACE2

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10.1126/science.abc1669Licence: CC BY

Cite this

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., ... Clevers, H. (2020). SARS-CoV-2 productively infects human gut enterocytes. Science, 369(6499), 50-54. https://doi.org/10.1126/science.abc1669

@article{a54247a0f7664229a8eff55c028c10bc,

title = "SARS-CoV-2 productively infects human gut enterocytes",

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 (hSlOs), 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 hSlOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSlOs serve as an experimental model for coronavirus infection and biology.",

keywords = "CORONAVIRUS, REPLICATION, EXPRESSION, ENTEROIDS, NETWORK, ACE2",

author = "Lamers, {Mart M} and Joep Beumer and {van der Vaart}, Jelte and K{\`e}vin Knoops and Jens Puschhof and Breugem, {Tim I} and Ravelli, {Raimond B G} and {Paul van Schayck}, J and Mykytyn, {Anna Z} and Duimel, {Hans Q} and {van Donselaar}, Elly and Samra Riesebosch and Kuijpers, {Helma J H} and Debby Schippers and {van de Wetering}, {Willine J} and {de Graaf}, Miranda and Marion Koopmans and Edwin Cuppen and Peters, {Peter J} and Haagmans, {Bart L} and Hans Clevers",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2020",

month = jul,

day = "3",

doi = "10.1126/science.abc1669",

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Lamers, MM, Beumer, J, van der Vaart, J, Knoops, K, Puschhof, J, Breugem, TI, Ravelli, RBG, Paul van Schayck, J, Mykytyn, AZ, Duimel, HQ, van Donselaar, E, Riesebosch, S, Kuijpers, HJH, Schippers, D, van de Wetering, WJ, de Graaf, M, Koopmans, M, Cuppen, E, Peters, PJ, Haagmans, BL & 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

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AU - Lamers, Mart M

AU - Beumer, Joep

AU - van der Vaart, Jelte

AU - Knoops, Kèvin

AU - Puschhof, Jens

AU - Breugem, Tim I

AU - Ravelli, Raimond B G

AU - Paul van Schayck, J

AU - Mykytyn, Anna Z

AU - Duimel, Hans Q

AU - van Donselaar, Elly

AU - Riesebosch, Samra

AU - Kuijpers, Helma J H

AU - Schippers, Debby

AU - van de Wetering, Willine J

AU - de Graaf, Miranda

AU - Koopmans, Marion

AU - Cuppen, Edwin

AU - Peters, Peter J

AU - Haagmans, Bart L

AU - Clevers, Hans

PY - 2020/7/3

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AB - 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 (hSlOs), 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 hSlOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSlOs serve as an experimental model for coronavirus infection and biology.

KW - CORONAVIRUS

KW - REPLICATION

KW - EXPRESSION

KW - ENTEROIDS

KW - NETWORK

KW - ACE2

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DO - 10.1126/science.abc1669

M3 - Article

C2 - 32358202

SN - 0036-8075

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SP - 50

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JF - Science

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