Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut.
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
Author Information
Sergio Triana: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. ORCID
Camila Metz-Zumaran: Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany. ORCID
Carlos Ramirez: Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, Germany.
Carmon Kee: Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
Patricio Doldan: Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
Mohammed Shahraz: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Daniel Schraivogel: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Andreas R Gschwind: Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Ashwini K Sharma: Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany. ORCID
Lars M Steinmetz: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Carl Herrmann: Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, Germany. ORCID
Theodore Alexandrov: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. ORCID
Steeve Boulant: Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
Megan L Stanifer: Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany. ORCID
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.
