TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes
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Open Access
- 19 May 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 5 (47)
- https://doi.org/10.1126/sciimmunol.abc3582
Abstract
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19. 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 patients with COVID-19. 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.Funding Information
- National Institutes of Health (R00 AI135031)
- National Institutes of Health (R01 AI150796)
- National Institutes of Health (R01 AI125249)
- National Institutes of Health (R01 AI127828)
- National Institutes of Health (75N93019C00062)
- National Institutes of Health (R37 AI059371)
- U.S. Department of Veterans Affairs (GRH0022)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK052574)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK109384)
- Defense Advanced Research Projects Agency (HR001117S0019)
- National Institute of Allergy and Infectious Diseases (F32 AI138392)
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