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TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.
Science Immunology ( IF 17.6 ) Pub Date : 2020-05-13 , DOI: 10.1126/sciimmunol.abc3582
Ruochen Zang 1 , Maria Florencia Gomez Castro 1 , Broc T McCune 1 , Qiru Zeng 1 , Paul W Rothlauf 1 , Naomi M Sonnek 1 , Zhuoming Liu 1 , Kevin F Brulois 1 , Xin Wang 1 , Harry B Greenberg 1 , Michael S Diamond 1 , Matthew A Ciorba 1 , Sean P J Whelan 1 , Siyuan Ding 1
Affiliation  

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.

中文翻译:


TMPRSS2 和 TMPRSS4 促进人小肠肠细胞的 SARS-CoV-2 感染。



在 COVID-19 患者中经常观察到胃肠道症状和 SARS-CoV-2 RNA 粪便排出。然而,尚不清楚 SARS-CoV-2 是否在人肠道中复制并导致可能的粪口传播。在这里,我们报告了 SARS-CoV-2 在人小肠肠类中 ACE2+ 成熟肠细胞中的有效感染。两种粘膜特异性丝氨酸蛋白酶 TMPRSS2 和 TMPRSS4 的表达促进了 SARS-CoV-2 尖峰融合活性并促进病毒进入宿主细胞。我们还证明,释放到肠腔中的病毒被模拟人结肠液灭活,并且没有从 COVID-19 患者的粪便标本中回收感染性病毒。我们的研究结果强调肠道是 SARS-CoV-2 复制的潜在位点,这可能导致局部和全身疾病以及整体疾病进展。
更新日期:2020-05-13
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