title: Replication of human noroviruses in stem cell-derived human enteroids.
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.
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Khalil
authors: K
authors: Ettayebi
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Sue E
authors: SE
authors: Crawford
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Kosuke
authors: K
authors: Murakami
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: James R
authors: JR
authors: Broughman
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Umesh
authors: U
authors: Karandikar
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Victoria R
authors: VR
authors: Tenge
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Frederick H
authors: FH
authors: Neill
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Sarah E
authors: SE
authors: Blutt
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Xi-Lei
authors: XL
authors: Zeng
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Lin
authors: L
authors: Qu
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Baijun
authors: B
authors: Kou
authors: 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.
authors: Antone R
authors: AR
authors: Opekun
authors: 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.
authors: Douglas
authors: D
authors: Burrin
authors: 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.
authors: David Y
authors: DY
authors: Graham
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors: Sasirekha
authors: S
authors: Ramani
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Robert L
authors: RL
authors: Atmar
authors: 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.
authors: Mary K
authors: MK
authors: Estes
mesh_terms: D001646:Bile; D017250:Caliciviridae Infections / Q000821:virology*; D018929:Cell Culture Techniques; D020895:Enterocytes / Q000821:virology; D005759:Gastroenteritis / Q000821:virology*; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology; D029322:Norovirus / Q000502:physiology*; D009940:Organoids / Q000821:virology*; D013234:Stem Cells / Q000821:virology; D014776:Virus Cultivation / Q000379:methods*; D014779:Virus Replication