Intestinal tuft cells are the physiologic target cell of murine norovirus and this tropism determines transkingdom interactions.. Tropism for tuft cells determines norovirus pathogenesis

The cellular tropism of noroviruses in immunocompetent hosts has long been unknown. Recently, we identified CD300lf as the receptor for murine norovirus (MNoV). Here we identify a rare type of intestinal epithelial cell called tuft cells as the physiologic target cell of MNoV in wild type animals. Viral tropism for tuft cells is determined by CD300lf expression. Type 2 immune cytokines (IL-4 and IL-25), which induce tuft cell proliferation, increase MNoV transmission, viral shedding during persistent infection, and can mimic the beneficial effect of commensal microbiota on virus infection. This is the first report of epithelial cell type specific viral infection and provides mechanistic insight into the transkingdom interactions of intestinal parasites, bacteria, viruses, and their mammalian hosts, which has important implications for enteric immunity and pathogenesis.