Sergio Triana1,2, Camila Metz-Zumaran3, Carlos Ramirez4, Carmon Kee3,5, Patricio Doldan3,5, Mohammed Shahraz1, Daniel Schraivogel6, Andreas R Gschwind7, Ashwini K Sharma3,4, Lars M Steinmetz6,7,8, Carl Herrmann4, Theodore Alexandrov1,9,10, Steeve Boulant3,5, Megan L Stanifer11. 1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. 2. Faculty of Biosciences, Collaboration for Joint PhD Degree between EMBL and Heidelberg University, Heidelberg, Germany. 3. Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany. 4. Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, Germany. 5. Research Group "Cellular Polarity and Viral Infection", German Cancer Research Center (DKFZ), Heidelberg, Germany. 6. Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. 7. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. 8. Stanford Genome Technology Center, Palo Alto, CA, USA. 9. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. 10. Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Heidelberg, Germany. 11. Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany.
Abstract
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 to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory 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 pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.
Exacerbated pro-iene">nflammatory immuene">ne respoene">nse coene">ntributes to n class="Disease">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 to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory 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 pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.
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