Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut

April 27, 2021

Sergio Triana, Camila Metz‐Zumaran, Carlos Ramirez, Carmon Kee, Patricio Doldan, Mohammed Shahraz, Daniel Schraivogel, Andreas R Gschwind, Ashwini K Sharma, Lars M Steinmetz, Carl Herrmann, Theodore Alexandrov, Steeve Boulant,Megan L Stanifer.

Mol Syst Biol

The analyses of single-cell of organoids to better understand the antiviral response the virus triggers in human intestinal epithelial cells (hIECs). The authors identified a subpopulation of enterocytes in the colon and ileum as the primary target of SARS-CoV-2 in hIECs. They then studied the virus’s impact on angiotensin-converting enzyme 2 (ACE2) and cellular protease type II transmembrane serine protease 2 (TMPRSS2) expression levels, as well as proinflammatory and interferon (IFN)-mediated responses, in infected cells and uninfected bystander cells. Cells with high levels of ACE2 were not particularly susceptible to SARS-CoV-2 infection, demonstrating that infection was not associated with high levels of ACE2; however, levels of TMPRSS2 were high in cells susceptible to SARS-CoV-2. Furthermore, ACE2 expression was found to negatively correlate to the presence of SARS-CoV-2. SARS-CoV-2 infection downregulated ACE2 expression in infected colon and ileum cells, as well as ileum bystander cells, but it did not affect ACE2 regulation in colon bystander cells. The study also found that infection generated a strong proinflammatory NFκB/TNF-mediated response in infected cells, while the bystander cells demonstrated a strong production of interferon-stimulated genes (ISGs) mediated by type III IFNs. Although infected cells secreted the IFNs that signaled to the bystander cells in a paracrine manner, SARS-CoV-2 shut down the cells’ own IFN-mediated signaling, meaning that the infected cells were unable to produce ISGs themselves.

Triana S, Metz-Zumaran C, Ramirez C, et al. Single‐cell analyses reveal SARS‐CoV‐2 interference with intrinsic immune response in the human gut. Mol Syst Biol (2021) 17:e10232.

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