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

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish
JournalScience immunology
Volume5
Issue number47
DOIs
StatePublished - May 13 2020

Fingerprint Dive into the research topics of 'TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes'. Together they form a unique fingerprint.

  • Cite this

    Zang, R., Gomez Castro, M. F., 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). https://doi.org/10.1126/sciimmunol.abc3582