TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

Ruochen Zang; Maria Florencia Gomez Castro; Broc T. McCune; Qiru Zeng; Paul W. Rothlauf; Naomi M. Sonnek; Zhuoming Liu; Kevin F. Brulois; Xin Wang; Harry B. Greenberg; Michael S. Diamond; Matthew A. Ciorba; Sean P.J. Whelan; Siyuan Ding

doi:10.1126/sciimmunol.abc3582

TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

Ruochen Zang, Maria Florencia Gomez Castro, Broc T. McCune, Qiru Zeng, Paul W. Rothlauf, Naomi M. Sonnek, Zhuoming Liu, Kevin F. Brulois, Xin Wang, Harry B. Greenberg, Michael S. Diamond, Matthew A. Ciorba, Sean P.J. Whelan, Siyuan Ding

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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.

Original language	English
Article number	eabc3582
Journal	Science immunology
Volume	5
Issue number	47
DOIs	https://doi.org/10.1126/sciimmunol.abc3582
State	Published - May 13 2020

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Zang, R., Castro, M. F. G., McCune, B. T., Zeng, Q., Rothlauf, P. W., Sonnek, N. M., Liu, Z., Brulois, K. F., Wang, X., Greenberg, H. B., Diamond, M. S., Ciorba, M. A., Whelan, S. P. J., & Ding, S. (2020). TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Science immunology, 5(47), Article eabc3582. https://doi.org/10.1126/sciimmunol.abc3582

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title = "TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes",

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.",

author = "Ruochen Zang and Castro, {Maria Florencia Gomez} and McCune, {Broc T.} and Qiru Zeng and Rothlauf, {Paul W.} and Sonnek, {Naomi M.} and Zhuoming Liu and Brulois, {Kevin F.} and Xin Wang and Greenberg, {Harry B.} and Diamond, {Michael S.} and Ciorba, {Matthew A.} and Whelan, {Sean P.J.} and Siyuan Ding",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved.",

year = "2020",

month = may,

day = "13",

doi = "10.1126/sciimmunol.abc3582",

language = "English",

volume = "5",

journal = "Science immunology",

issn = "2470-9468",

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T1 - TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

AU - Zang, Ruochen

AU - Castro, Maria Florencia Gomez

AU - McCune, Broc T.

AU - Zeng, Qiru

AU - Rothlauf, Paul W.

AU - Sonnek, Naomi M.

AU - Liu, Zhuoming

AU - Brulois, Kevin F.

AU - Wang, Xin

AU - Greenberg, Harry B.

AU - Diamond, Michael S.

AU - Ciorba, Matthew A.

AU - Whelan, Sean P.J.

AU - Ding, Siyuan

PY - 2020/5/13

Y1 - 2020/5/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85084625747&partnerID=8YFLogxK

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DO - 10.1126/sciimmunol.abc3582

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AN - SCOPUS:85084625747

SN - 2470-9468

VL - 5

JO - Science immunology

JF - Science immunology

IS - 47

M1 - eabc3582

ER -

TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

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