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

Sergio Triana, Camila Metz Zumaran, Carlos Ramirez, Carmon Kee, Patricio Doldan, Mohammed Shahraz, Daniel Schraivogel, Andreas R. Gschwind, Lars M. Steinmetz, Carl Herrmann, Theodore Alexandrov, Steeve Boulant (+1 others)
2020 bioRxiv   pre-print
Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility
more » ... o infection and the expression of ACE2. Infected cells activated strong proinflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a proinflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.
doi:10.1101/2020.10.21.348854 fatcat:3kbebigebnb5zj337cu5ivx67a