Robust and persistent SARS-CoV-2 infection in the human intestinal brush border expressing cells

• Published in: Emerging microbes & infections Vol. 9; no. 1; pp. 2169 - 2179
• Main Authors: Lee, Sunhee, Yoon, Gun Young, Myoung, Jinjong, Kim, Seong-Jun, Ahn, Dae-Gyun
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2020; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Betacoronavirus - genetics; Betacoronavirus - physiology; Cell Line; coronavirus; Coronavirus Infections - genetics; Coronavirus Infections - metabolism; Coronavirus Infections - virology; Coronaviruses; COVID-19; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - virology; Humans; Infections; Intestinal Mucosa - metabolism; Intestinal Mucosa - virology; Pandemics; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; persistent; Pneumonia, Viral - genetics; Pneumonia, Viral - metabolism; Pneumonia, Viral - virology; Receptors, Virus - genetics; Receptors, Virus - metabolism; SARS-CoV-2; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Severe acute respiratory syndrome coronavirus 2; COVID-19; ACE2; coronavirus; SARS-CoV-2; persistent
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2020.1827985

Studies on patients with the coronavirus disease-2019 (COVID-19) have implicated that the gastrointestinal (GI) tract is a major site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established a human GI tract cell line model highly permissive to SARS-CoV-2. These cells, C2BBe1 intestinal cells with a brush border having high levels of transmembrane serine protease 2 (TMPRSS2), showed robust viral propagation, and could be persistently infected with SARS-CoV-2, supporting the clinical observations of persistent GI infection in COVID-19 patients. Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation. Thus, our study sheds light on the pathogenesis of SARS-CoV-2 in the GI tract.