TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes
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(+)...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285829/ https://www.ncbi.nlm.nih.gov/pubmed/32404436 http://dx.doi.org/10.1126/sciimmunol.abc3582 |
_version_ | 1783544773381980160 |
---|---|
author | Zang, Ruochen Gomez Castro, Maria Florencia McCune, Broc T. Zeng, Qiru Rothlauf, Paul W. Sonnek, Naomi M. Liu, Zhuoming Brulois, Kevin F. Wang, Xin Greenberg, Harry B. Diamond, Michael S. Ciorba, Matthew A. Whelan, Sean P. J. Ding, Siyuan |
author_facet | Zang, Ruochen Gomez Castro, Maria Florencia McCune, Broc T. Zeng, Qiru Rothlauf, Paul W. Sonnek, Naomi M. Liu, Zhuoming Brulois, Kevin F. Wang, Xin Greenberg, Harry B. Diamond, Michael S. Ciorba, Matthew A. Whelan, Sean P. J. Ding, Siyuan |
author_sort | Zang, Ruochen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7285829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-72858292020-06-12 TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes Zang, Ruochen Gomez Castro, Maria Florencia McCune, Broc T. Zeng, Qiru Rothlauf, Paul W. Sonnek, Naomi M. Liu, Zhuoming Brulois, Kevin F. Wang, Xin Greenberg, Harry B. Diamond, Michael S. Ciorba, Matthew A. Whelan, Sean P. J. Ding, Siyuan Sci Immunol Research Articles 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. American Association for the Advancement of Science 2020-05-13 /pmc/articles/PMC7285829/ /pubmed/32404436 http://dx.doi.org/10.1126/sciimmunol.abc3582 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Zang, Ruochen Gomez Castro, Maria Florencia McCune, Broc T. Zeng, Qiru Rothlauf, Paul W. Sonnek, Naomi M. Liu, Zhuoming Brulois, Kevin F. Wang, Xin Greenberg, Harry B. Diamond, Michael S. Ciorba, Matthew A. Whelan, Sean P. J. Ding, Siyuan TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title | TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title_full | TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title_fullStr | TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title_full_unstemmed | TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title_short | TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes |
title_sort | tmprss2 and tmprss4 promote sars-cov-2 infection of human small intestinal enterocytes |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285829/ https://www.ncbi.nlm.nih.gov/pubmed/32404436 http://dx.doi.org/10.1126/sciimmunol.abc3582 |
work_keys_str_mv | AT zangruochen tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT gomezcastromariaflorencia tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT mccunebroct tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT zengqiru tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT rothlaufpaulw tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT sonneknaomim tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT liuzhuoming tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT bruloiskevinf tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT wangxin tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT greenbergharryb tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT diamondmichaels tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT ciorbamatthewa tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT whelanseanpj tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes AT dingsiyuan tmprss2andtmprss4promotesarscov2infectionofhumansmallintestinalenterocytes |