Single-cell profiling of the duodenum during chronic human norovirus infection.

Single-cell RNA-seq of duodenal biopsies from immunodeficient individuals with chronic human norovirus infection shows viral RNA is most enriched in M2 macrophages, then late enterocytes.

• Why it matters: Norovirus pathogenesis is poorly defined, and chronic infection offers a chance to map which duodenal cell types harbor virus and how immunity shifts at single-cell resolution.
• What they did: The study profiled duodenal biopsies by single-cell RNA sequencing and matched stem cell-derived enteroids, then quantified viral RNA-positive cells and compared in vitro viral yields across cell types.
• The result: Infection is linked to increased MHC class I-related genes and IL15 in macrophages and late enterocytes, higher IFNG in CD8 T cells, and CXCL9 plus CXCL10/11 up-regulation, implying coordinated innate–adaptive immune dysregulation.

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