TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.
Identifieur interne : 000249 ( Main/Exploration ); précédent : 000248; suivant : 000250TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.
Auteurs : Ruochen Zang [États-Unis] ; Maria Florencia Gomez Castro [États-Unis] ; Broc T. Mccune [États-Unis] ; Qiru Zeng [États-Unis] ; Paul W. Rothlauf [États-Unis] ; Naomi M. Sonnek [États-Unis] ; Zhuoming Liu [États-Unis] ; Kevin F. Brulois [États-Unis] ; Xin Wang [États-Unis] ; Harry B. Greenberg [États-Unis] ; Michael S. Diamond [États-Unis] ; Matthew A. Ciorba [États-Unis] ; Sean P J. Whelan [États-Unis] ; Siyuan Ding [États-Unis]Source :
- Science immunology [ 2470-9468 ] ; 2020.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Betacoronavirus (physiologie), Duodénum (cytologie), Entérocytes (anatomopathologie), Entérocytes (virologie), Humains (MeSH), Lignée cellulaire (MeSH), Organoïdes (virologie), Peptidyl-Dipeptidase A (métabolisme), Protéines membranaires (métabolisme), Pénétration virale (MeSH), Rotavirus (physiologie), Serine endopeptidases (métabolisme), Souris (MeSH), Vesiculovirus (génétique).
- MESH :
- anatomopathologie : Entérocytes.
- cytologie : Duodénum.
- génétique : Vesiculovirus.
- métabolisme : Peptidyl-Dipeptidase A, Protéines membranaires, Serine endopeptidases.
- physiologie : Betacoronavirus, Rotavirus.
- virologie : Entérocytes, Organoïdes.
- Animaux, Humains, Lignée cellulaire, Pénétration virale, Souris.
English descriptors
- KwdEn :
- Angiotensin-Converting Enzyme 2 (MeSH), Animals (MeSH), Betacoronavirus (physiology), Cell Line (MeSH), Duodenum (cytology), Enterocytes (pathology), Enterocytes (virology), Humans (MeSH), Membrane Proteins (metabolism), Mice (MeSH), Organoids (virology), Peptidyl-Dipeptidase A (metabolism), Rotavirus (physiology), SARS-CoV-2 (MeSH), Serine Endopeptidases (metabolism), Vesiculovirus (genetics), Virus Internalization (MeSH).
- MESH :
- chemical , metabolism : Membrane Proteins, Peptidyl-Dipeptidase A, Serine Endopeptidases.
- chemical : Angiotensin-Converting Enzyme 2.
- cytology : Duodenum.
- genetics : Vesiculovirus.
- pathology : Enterocytes.
- physiology : Betacoronavirus, Rotavirus.
- virology : Enterocytes, Organoids.
- Animals, Cell Line, Humans, Mice, SARS-CoV-2, Virus Internalization.
Abstract
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.
DOI: 10.1126/sciimmunol.abc3582
PubMed: 32404436
PubMed Central: PMC7285829
Affiliations:
- États-Unis
- Missouri (État)
- Saint-Louis (Missouri)
- École de médecine (Université Washington de Saint-Louis)
Links toward previous steps (curation, corpus...)
Le document en format XML
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Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Gomez Castro, Maria Florencia" sort="Gomez Castro, Maria Florencia" uniqKey="Gomez Castro M" first="Maria Florencia" last="Gomez Castro">Maria Florencia Gomez Castro</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Mccune, Broc T" sort="Mccune, Broc T" uniqKey="Mccune B" first="Broc T" last="Mccune">Broc T. Mccune</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Zeng, Qiru" sort="Zeng, Qiru" uniqKey="Zeng Q" first="Qiru" last="Zeng">Qiru Zeng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Rothlauf, Paul W" sort="Rothlauf, Paul W" uniqKey="Rothlauf P" first="Paul W" last="Rothlauf">Paul W. Rothlauf</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Sonnek, Naomi M" sort="Sonnek, Naomi M" uniqKey="Sonnek N" first="Naomi M" last="Sonnek">Naomi M. Sonnek</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Liu, Zhuoming" sort="Liu, Zhuoming" uniqKey="Liu Z" first="Zhuoming" last="Liu">Zhuoming Liu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Brulois, Kevin F" sort="Brulois, Kevin F" uniqKey="Brulois K" first="Kevin F" last="Brulois">Kevin F. Brulois</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Greenberg, Harry B" sort="Greenberg, Harry B" uniqKey="Greenberg H" first="Harry B" last="Greenberg">Harry B. Greenberg</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Diamond, Michael S" sort="Diamond, Michael S" uniqKey="Diamond M" first="Michael S" last="Diamond">Michael S. Diamond</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Ciorba, Matthew A" sort="Ciorba, Matthew A" uniqKey="Ciorba M" first="Matthew A" last="Ciorba">Matthew A. Ciorba</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Whelan, Sean P J" sort="Whelan, Sean P J" uniqKey="Whelan S" first="Sean P J" last="Whelan">Sean P J. Whelan</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Ding, Siyuan" sort="Ding, Siyuan" uniqKey="Ding S" first="Siyuan" last="Ding">Siyuan Ding</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. siyuan.ding@wustl.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32404436</idno><idno type="pmid">32404436</idno><idno type="doi">10.1126/sciimmunol.abc3582</idno><idno type="pmc">PMC7285829</idno><idno type="wicri:Area/Main/Corpus">000727</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000727</idno><idno type="wicri:Area/Main/Curation">000727</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000727</idno><idno type="wicri:Area/Main/Exploration">000727</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.</title><author><name sortKey="Zang, Ruochen" sort="Zang, Ruochen" uniqKey="Zang R" first="Ruochen" last="Zang">Ruochen Zang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Gomez Castro, Maria Florencia" sort="Gomez Castro, Maria Florencia" uniqKey="Gomez Castro M" first="Maria Florencia" last="Gomez Castro">Maria Florencia Gomez Castro</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Mccune, Broc T" sort="Mccune, Broc T" uniqKey="Mccune B" first="Broc T" last="Mccune">Broc T. Mccune</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Zeng, Qiru" sort="Zeng, Qiru" uniqKey="Zeng Q" first="Qiru" last="Zeng">Qiru Zeng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Rothlauf, Paul W" sort="Rothlauf, Paul W" uniqKey="Rothlauf P" first="Paul W" last="Rothlauf">Paul W. Rothlauf</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Sonnek, Naomi M" sort="Sonnek, Naomi M" uniqKey="Sonnek N" first="Naomi M" last="Sonnek">Naomi M. Sonnek</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Liu, Zhuoming" sort="Liu, Zhuoming" uniqKey="Liu Z" first="Zhuoming" last="Liu">Zhuoming Liu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Brulois, Kevin F" sort="Brulois, Kevin F" uniqKey="Brulois K" first="Kevin F" last="Brulois">Kevin F. Brulois</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Greenberg, Harry B" sort="Greenberg, Harry B" uniqKey="Greenberg H" first="Harry B" last="Greenberg">Harry B. Greenberg</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Diamond, Michael S" sort="Diamond, Michael S" uniqKey="Diamond M" first="Michael S" last="Diamond">Michael S. Diamond</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Ciorba, Matthew A" sort="Ciorba, Matthew A" uniqKey="Ciorba M" first="Matthew A" last="Ciorba">Matthew A. Ciorba</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Whelan, Sean P J" sort="Whelan, Sean P J" uniqKey="Whelan S" first="Sean P J" last="Whelan">Sean P J. Whelan</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author><author><name sortKey="Ding, Siyuan" sort="Ding, Siyuan" uniqKey="Ding S" first="Siyuan" last="Ding">Siyuan Ding</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. siyuan.ding@wustl.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region><settlement type="city">Saint-Louis (Missouri)</settlement></placeName><orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName></affiliation></author></analytic><series><title level="j">Science immunology</title><idno type="eISSN">2470-9468</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiotensin-Converting Enzyme 2 (MeSH)</term><term>Animals (MeSH)</term><term>Betacoronavirus (physiology)</term><term>Cell Line (MeSH)</term><term>Duodenum (cytology)</term><term>Enterocytes (pathology)</term><term>Enterocytes (virology)</term><term>Humans (MeSH)</term><term>Membrane Proteins (metabolism)</term><term>Mice (MeSH)</term><term>Organoids (virology)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>Rotavirus (physiology)</term><term>SARS-CoV-2 (MeSH)</term><term>Serine Endopeptidases (metabolism)</term><term>Vesiculovirus (genetics)</term><term>Virus Internalization (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Betacoronavirus (physiologie)</term><term>Duodénum (cytologie)</term><term>Entérocytes (anatomopathologie)</term><term>Entérocytes (virologie)</term><term>Humains (MeSH)</term><term>Lignée cellulaire (MeSH)</term><term>Organoïdes (virologie)</term><term>Peptidyl-Dipeptidase A (métabolisme)</term><term>Protéines membranaires (métabolisme)</term><term>Pénétration virale (MeSH)</term><term>Rotavirus (physiologie)</term><term>Serine endopeptidases (métabolisme)</term><term>Souris (MeSH)</term><term>Vesiculovirus (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Proteins</term><term>Peptidyl-Dipeptidase A</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Angiotensin-Converting Enzyme 2</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Entérocytes</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Duodénum</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Duodenum</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Vesiculovirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Vesiculovirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term><term>Protéines membranaires</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Enterocytes</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Betacoronavirus</term><term>Rotavirus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Betacoronavirus</term><term>Rotavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Entérocytes</term><term>Organoïdes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Enterocytes</term><term>Organoids</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Mice</term><term>SARS-CoV-2</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Lignée cellulaire</term><term>Pénétration virale</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2<sup>+</sup> mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32404436</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>18</Day></DateCompleted><DateRevised><Year>2020</Year><Month>12</Month><Day>18</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2470-9468</ISSN><JournalIssue CitedMedium="Internet"><Volume>5</Volume><Issue>47</Issue><PubDate><Year>2020</Year><Month>05</Month><Day>13</Day></PubDate></JournalIssue><Title>Science immunology</Title><ISOAbbreviation>Sci Immunol</ISOAbbreviation></Journal><ArticleTitle>TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">eabc3582</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1126/sciimmunol.abc3582</ELocationID><Abstract><AbstractText>Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2<sup>+</sup> mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.</AbstractText><CopyrightInformation>Copyright © 2020, The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zang</LastName><ForeName>Ruochen</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gomez Castro</LastName><ForeName>Maria Florencia</ForeName><Initials>MF</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCune</LastName><ForeName>Broc T</ForeName><Initials>BT</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeng</LastName><ForeName>Qiru</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rothlauf</LastName><ForeName>Paul W</ForeName><Initials>PW</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sonnek</LastName><ForeName>Naomi M</ForeName><Initials>NM</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Zhuoming</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brulois</LastName><ForeName>Kevin F</ForeName><Initials>KF</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Greenberg</LastName><ForeName>Harry B</ForeName><Initials>HB</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diamond</LastName><ForeName>Michael S</ForeName><Initials>MS</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ciorba</LastName><ForeName>Matthew A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Whelan</LastName><ForeName>Sean P J</ForeName><Initials>SPJ</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Siyuan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China. Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA. Program in Virology, Harvard Medical School, 200 Longwood Ave, Boston, MA, USA. Department of Medicine, Division of Gastroenterology, Washington School of Medicine, St. Louis, MO, USA. Department of Pathology, Stanford School of Medicine, Stanford, CA, USA. VA Palo Alto Health Care System, Department of Veterans Affairs, Palo Alto, CA, USA. Department of Medicine, Division of Gastroenterology and Hepatology, and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, CA, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. siyuan.ding@wustl.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R00 AI135031</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K99 AI135031</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F32 AI138392</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>TL1 TR002344</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>S10 OD020141</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI150796</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United 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Mccune</name><name sortKey="Rothlauf, Paul W" sort="Rothlauf, Paul W" uniqKey="Rothlauf P" first="Paul W" last="Rothlauf">Paul W. Rothlauf</name><name sortKey="Sonnek, Naomi M" sort="Sonnek, Naomi M" uniqKey="Sonnek N" first="Naomi M" last="Sonnek">Naomi M. Sonnek</name><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><name sortKey="Whelan, Sean P J" sort="Whelan, Sean P J" uniqKey="Whelan S" first="Sean P J" last="Whelan">Sean P J. Whelan</name><name sortKey="Zeng, Qiru" sort="Zeng, Qiru" uniqKey="Zeng Q" first="Qiru" last="Zeng">Qiru Zeng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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