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 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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Document Details

Document Type
Technical Report
Publication Date
May 13, 2020
Accession Number
AD1099338

Entities

People

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

Organizations

  • University of Washington

Tags

DTIC Thesaurus Topics

  • Cell Physiological Processes
  • Covid-19
  • Culture Techniques
  • Disease Outbreaks
  • Epithelial Cells
  • Health Services
  • Infectious Diseases
  • Interferon
  • Mers-Cov
  • Microbiology
  • Mucous Membrane
  • Sars
  • Virology
  • Virus Diseases
  • Viruses
  • Zoonoses

Fields of Study

  • Biology

Readers

  • Immunology and Pathology
  • Infectious Disease/Epidemiology
  • Microbial Pathology