TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes
Ruochen Zang, María Florencia Gómez Castro, Broc T. McCune, Qiru Zeng, Paul W. Rothlauf, Naomi Sonnek, Zhuoming Liu, Kevin Brulois, Xin Wang, Harry B. Greenberg, Michael Diamond, Matthew A. Ciorba, Sean P. J. Whelan, Siyuan Ding
Abstract
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.