Single-cell profiling of the duodenum during chronic human norovirus infection
Year: 2026
Type: article
Abstract: Human noroviruses are a major cause of diarrheal disease, yet their pathogenesis remains poorly defined. We performed single-cell RNA sequencing of duodenal biopsies and matched stem cell–derived enteroids from immunodeficient individuals with chronic norovirus infection. Norovirus RNA was detected primarily in enterocytes, enteroendocrine cells, and macrophages, with the highest proportion of viral RNA-positive cells observed among M2 macrophages, followed by late enterocytes. Despite this distribution, late enterocytes produced higher viral yields than differentiated M2 macrophages in vitro. Norovirus infection was associated with the up-regulation of MHC class I-related genes and IL15 in duodenal macrophages and late enterocytes, together with increased IFNG expression by CD8 T cells. Macrophages and late enterocytes up-regulated CXCL9 and CXCL10/11 , respectively, consistent with CD8 and CD4 T cell recruitment to the duodenum. These findings show that noroviruses infect and persist across multiple permissive cell types during chronic infection, resulting in marked dysregulation of innate and adaptive immune responses that may drive pathogenesis.
Source: Science Advances
Authors: Yuki Matsushima, Jessica Durkee-Shock, Derron A. Alves, Bianca M. Nagata, Sun A. Kim, Eunice C. Chan, Natthawan Chaimongkol, Ryoka Ishiyama, Karenna Barton, Alison Han, Libby A. Kelly, Princess U. Ogbogu, Sheila Kumar, Xixi Xu, Kristi C. Briggs, Kosuke Murakami, Jeffrey I. Cohen, Michael D. Keller, Stanislav V. Sosnovtsev, Kim Y. Green
Institutions: National Institutes of Health, National Institute of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Japan Institute for Health Security, National Cancer Institute, Center for Cancer Research, Intermountain Healthcare, University Hospitals of Cleveland, University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital, Case Western Reserve University, National Institute of Diabetes and Digestive and Kidney Diseases, Children's National
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W7225785010