Format

Send to

Choose Destination
Science. 2016 Sep 23;353(6306):1387-1393. Epub 2016 Aug 25.

Replication of human noroviruses in stem cell-derived human enteroids.

Author information

1
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
2
Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
3
Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
4
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
5
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
6
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. Department of Medicine, Baylor College of Medicine, Houston, TX, USA. mestes@bcm.edu.

Abstract

The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the leading cause of gastroenteritis worldwide. We report the successful cultivation of multiple HuNoV strains in enterocytes in stem cell-derived, nontransformed human intestinal enteroid monolayer cultures. Bile, a critical factor of the intestinal milieu, is required for strain-dependent HuNoV replication. Lack of appropriate histoblood group antigen expression in intestinal cells restricts virus replication, and infectivity is abrogated by inactivation (e.g., irradiation, heating) and serum neutralization. This culture system recapitulates the human intestinal epithelium, permits human host-pathogen studies of previously noncultivatable pathogens, and allows the assessment of methods to prevent and treat HuNoV infections.

PMID:
27562956
PMCID:
PMC5305121
DOI:
10.1126/science.aaf5211
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center