@article{1751, author = {Ruochen Zang and Maria Florencia Gomez Castro and Broc T. McCune and Qiru Zeng and Paul W. Rothlauf and Naomi M. Sonnek and Zhuoming Liu and Kevin F. Brulois and Xin Wang and Harry B. Greenberg and Michael S. Diamond and Matthew A. Ciorba and Sean P. J. Whelan and Siyuan Ding}, title = {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. 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 patients with COVID-19. 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.}, year = {2020}, journal = {Science Immunology}, volume = {5}, pages = {eabc3582}, month = {2020-05-13}, url = {https://www.science.org/doi/10.1126/sciimmunol.abc3582}, doi = {10.1126/sciimmunol.abc3582}, }