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In Vitro Replication of Human Norovirus
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Human Norovirus Cultivation in Nontransformed Stem Cell-Derived Human Intestinal Enteroid Cultures: Success and Challenges

1
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
2
Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA
3
Department of Medicine, Infectious Diseases, Baylor College of Medicine, Houston, TX 77030, USA
4
Department of Virology II, National Institute of Infectious Diseases, Musashi-murayama, Tokyo 208-0011, Japan
*
Author to whom correspondence should be addressed.
Current address: Department of Medicine, Infectious Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Viruses 2019, 11(7), 638; https://doi.org/10.3390/v11070638
Received: 11 June 2019 / Revised: 1 July 2019 / Accepted: 4 July 2019 / Published: 11 July 2019
(This article belongs to the Special Issue Noroviruses)
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Abstract

Noroviruses, in the genus Norovirus, are a significant cause of viral gastroenteritis in humans and animals. For almost 50 years, the lack of a cultivation system for human noroviruses (HuNoVs) was a major barrier to understanding virus biology and the development of effective antiviral strategies. This review presents a historical perspective of the development of a cultivation system for HuNoVs in human intestinal epithelial cell cultures. Successful cultivation was based on the discovery of genetically-encoded host factors required for infection, knowledge of the site of infection in humans, and advances in the cultivation of human intestinal epithelial cells achieved by developmental and stem cell biologists. The human stem cell-derived enteroid cultivation system recapitulates the multicellular, physiologically active human intestinal epithelium, and allows studies of virus-specific replication requirements, evaluation of human host-pathogen interactions, and supports the pre-clinical assessment of methods to prevent and treat HuNoV infections. View Full-Text
Keywords: human norovirus cultivation; intestinal enteroids/organoids; virus neutralization and inactivation human norovirus cultivation; intestinal enteroids/organoids; virus neutralization and inactivation
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Estes, M.K.; Ettayebi, K.; Tenge, V.R.; Murakami, K.; Karandikar, U.; Lin, S.-C.; Ayyar, B.V.; Cortes-Penfield, N.W.; Haga, K.; Neill, F.H.; Opekun, A.R.; Broughman, J.R.; Zeng, X.-L.; Blutt, S.E.; Crawford, S.E.; Ramani, S.; Graham, D.Y.; Atmar, R.L. Human Norovirus Cultivation in Nontransformed Stem Cell-Derived Human Intestinal Enteroid Cultures: Success and Challenges. Viruses 2019, 11, 638.

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