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

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

1231 Citations (Scopus)

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.

Original language	English
Pages (from-to)	50-54
Number of pages	5
Journal	Science
Volume	369
Issue number	6499
DOIs	https://doi.org/10.1126/science.abc1669
Publication status	Published - 03 Jul 2020

Keywords

Angiotensin-Converting Enzyme 2
Betacoronavirus/physiology
Cell Culture Techniques
Cell Differentiation
Cell Lineage
Cell Proliferation
Culture Media
Enterocytes/metabolism
Gene Expression
Humans
Ileum/metabolism
Lung/virology
Male
Organoids
Peptidyl-Dipeptidase A/genetics
RNA, Messenger/genetics
Receptors, Virus/genetics
Respiratory Mucosa/virology
SARS Virus/physiology
SARS-CoV-2
Virus Replication

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10.1126/science.abc1669

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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., Schipper, 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

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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 (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.",

keywords = "Angiotensin-Converting Enzyme 2, Betacoronavirus/physiology, Cell Culture Techniques, Cell Differentiation, Cell Lineage, Cell Proliferation, Culture Media, Enterocytes/metabolism, Gene Expression, Humans, Ileum/metabolism, Lung/virology, Male, Organoids, Peptidyl-Dipeptidase A/genetics, RNA, Messenger/genetics, Receptors, Virus/genetics, Respiratory Mucosa/virology, SARS Virus/physiology, SARS-CoV-2, Virus Replication",

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 Schipper 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, American Association for the Advancement of Science.",

year = "2020",

month = jul,

day = "3",

doi = "10.1126/science.abc1669",

language = "English",

volume = "369",

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journal = "Science",

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publisher = "American Association for the Advancement of Science (AAAS)",

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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, Schipper, 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

TY - JOUR

T1 - SARS-CoV-2 productively infects human gut enterocytes

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 - Schipper, 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

Y1 - 2020/7/3

N2 - 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.

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 (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.

KW - Angiotensin-Converting Enzyme 2

KW - Betacoronavirus/physiology

KW - Cell Culture Techniques

KW - Cell Differentiation

KW - Cell Lineage

KW - Cell Proliferation

KW - Culture Media

KW - Enterocytes/metabolism

KW - Gene Expression

KW - Humans

KW - Ileum/metabolism

KW - Lung/virology

KW - Male

KW - Organoids

KW - Peptidyl-Dipeptidase A/genetics

KW - RNA, Messenger/genetics

KW - Receptors, Virus/genetics

KW - Respiratory Mucosa/virology

KW - SARS Virus/physiology

KW - SARS-CoV-2

KW - Virus Replication

U2 - 10.1126/science.abc1669

DO - 10.1126/science.abc1669

M3 - Article

C2 - 32358202

SN - 0036-8075

VL - 369

SP - 50

EP - 54

JO - Science

JF - Science

IS - 6499

ER -

SARS-CoV-2 productively infects human gut enterocytes

Abstract

Keywords

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