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(+)...

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Autores principales: 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
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
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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.
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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
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