Single-cell sequencing of rotavirus-infected intestinal epithelium reveals cell-type specific epithelial repair and tuft cell infection

Significance Rotavirus infects enterocytes at the tips of intestinal villi, leading to damage. Single-cell RNA sequencing of the infected murine intestinal epithelium reveals broad responses, including expansion of the stem cell and immature enterocyte populations. Subsets of stem cells enter the cell cycle more frequently, resulting in production of more enterocytes to compensate for damaged enterocytes at the villus tip. The presence of viral transcripts in tuft cells and evidence of tuft cell transcriptional activation suggests that tuft cells contribute important signals to the epithelial response following damage. Until now the mechanism of repair following viral damage in the intestinal epithelium has remained uncharacterized. We find that intestinal regeneration and repair require cooperation of several specialized epithelial cells.