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bioRxiv · 10.1101/2020.08.19.255893

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

Triana, S.·Stanifer, M. L.·Shahraz, M.·Mukenhirn, M.·Kee, C.·Ordonez Rueda, D.·Paulsen, M.·Benes, V.·Boulant, S.·Alexandrov, T.
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Abstract

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.

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Triana, S., Stanifer, M. L., Shahraz, M., Mukenhirn, M., Kee, C., Ordonez Rueda, D., Paulsen, M., Benes, V., Boulant, S., Alexandrov, T.. 2020-08-19. Single-cell transcriptomics reveals immune response of intestinal cell types to viral infection. https://doi.org/10.1101/2020.08.19.255893

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