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

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.

• UD
  U.S. Department of Veterans Affairs

  Award: GRH0022
• NI
  National Institutes of Health

  Awards: R37 AI059371, R01 AI150796, 75N93019C00062, R01 AI125249, R01 AI127828, R00 AI135031
• DA
  Defense Advanced Research Projects Agency

  Award: HR001117S0019
• NI
  National Institute of Allergy and Infectious Diseases

  Award: F32 AI138392
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: P30 DK052574, R01 DK109384