Replication of human noroviruses in stem cell-derived human enteroids

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 strain...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 353; no. 6306; pp. 1387 - 1393
Main Authors:	Ettayebi, Khalil, Crawford, Sue E., Murakami, Kosuke, Broughman, James R., Karandikar, Umesh, Tenge, Victoria R., Neill, Frederick H., Blutt, Sarah E., Zeng, Xi-Lei, Qu, Lin, Kou, Baijun, Opekun, Antone R., Burrin, Douglas, Graham, David Y., Ramani, Sasirekha, Atmar, Robert L., Estes, Mary K.
Format:	Journal Article
Language:	English
Published:	United States American Association for the Advancement of Science 23-09-2016 The American Association for the Advancement of Science
Subjects:	Antigens Assessments Bile Caliciviridae Infections - virology Cell Culture Techniques Cultivation Culture Enterocytes - virology Epithelium Gastroenteritis - virology Gastroenterology Humans Intestinal Mucosa - virology Norovirus - physiology Organoids - virology Pathogens Replication Stem cells Stem Cells - virology Virus Cultivation - methods Virus Replication Viruses
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Summary:	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 straindependent 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 co-first authors
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.aaf5211