01686nas a2200289   4500000000100000008004100001260001500042100001700057700003300074700001900107700001400126700002100140700002000161700001700181700002100198700001300219700002300232700002300255700002200278700002200300700001600322245009100338856005900429300001300488490000600501520088900507       2020                            d  c2020-05-131 aRuochen Zang1 aMaria Florencia Gomez Castro1 aBroc T. McCune1 aQiru Zeng1 aPaul W. Rothlauf1 aNaomi M. Sonnek1 aZhuoming Liu1 aKevin F. Brulois1 aXin Wang1 aHarry B. Greenberg1 aMichael S. Diamond1 aMatthew A. Ciorba1 aSean P. J. Whelan1 aSiyuan Ding00aTMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes  uhttps://www.science.org/doi/10.1126/sciimmunol.abc3582  aeabc35820 v53 aGastrointestinal 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.