Research ArticleCORONAVIRUS

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

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Science Immunology  13 May 2020:
Vol. 5, Issue 47, eabc3582
DOI: 10.1126/sciimmunol.abc3582

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Smothering fecal-oral coronavirus spread

Besides respiratory symptoms, diarrhea is one of the other commonly observed disease manifestations in patients with COVID-19. Zang et al. used organoid cultures of epithelial lining cells from human small and large intestine as an in vitro model system to study SARS-CoV-2 entry and replication in enterocytes. Mature enterocytes expressing the highest levels of the angiotensin-converting enzyme 2 (ACE2) viral receptor were susceptible to productive infection. Two related membrane-bound serine proteases, TMPRSS2 and TMPRSS4, enhanced virus entry into enterocytes. While a subset of patients with COVID-19 shed high levels of viral RNA in feces, experiments examining the effect of simulated human colonic fluid on the virus suggest that shed virus is rapidly inactivated during transit through the colon, strongly suppressing the potential for further spread of the infection through a fecal-oral route.

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