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

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.

Authors

Institutions

Publication Details

Journal
Science Advances
Published
2026-11-11
DOI
https://doi.org/10.1126/sciadv.aej2676
Primary Topic
Viral gastroenteritis research and epidemiology
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
NOV
article

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

Kristi Briggs, Michael Daniel Keller, Kosuke Murakami, Derron A. Alves et al.
Science Advances
Viral gastroenteritis research and epidemiology
article

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

Kristi Briggs, Michael Daniel Keller, Kosuke Murakami, Derron A. Alves, Jeffrey I. Cohen, Stanislav V. Sosnovtsev, Alison Han, Ryoka Ishiyama, Sheila Kumar, Princess U. Ogbogu, Kim N. Green, Bianca M. Nagata, Libby A. Kelly, Jessica R. Durkee-Shock, Sun A. Kim, Eunice Ching Chan, Natthawan Chaimongkol, Karenna Barton, Xixi Xu, Yuki Matsushima
article en

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.

Science AdvancesVol. 12(46)
Intermountain Healthcare (US), National Institutes of Health (US), Children's National (US), University Hospitals of Cleveland (US), National Institute of Infectious Diseases (JP), National Institute of Diabetes and Digestive and Kidney Diseases (US), University Hospitals Cleveland Medical Center (US), National Institute of Allergy and Infectious Diseases (US), National Cancer Institute (US), Center for Cancer Research (US), Rainbow Babies & Children's Hospital (US), Japan Institute for Health Security (JP), Case Western Reserve University (US)
Viral gastroenteritis research and epidemiology
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Laika access coming soon