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Single-cell transcriptomics reveals immune response of intestinal cell types to viral infection

By Sergio H Triana, Megan Stanifer, Mohammed Shahraz, Markus Mukenhirn, Carmon Kee, Diana Ordonez Rueda, Malte Paulsen, Vladimit Benes, Steeve Boulant, Theodore Alexandrov

Posted 19 Aug 2020
bioRxiv DOI: 10.1101/2020.08.19.255893

Human intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a pipeline combining single-cell RNA-Seq and highly-multiplex RNA imaging and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages with a preferential infection of proliferating cells. Intriguingly, each intestinal epithelial cell lineage has a unique basal expression of interferon-stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon-stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our pipeline can be applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis. ### Competing Interest Statement The authors have declared no competing interest.

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