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

Mary K. Estes, Khalil Ettayebi, Victoria R. Tenge, Kosuke Murakami, Umesh Karandikar, Shih Ching Lin, B. Vijayalakshmi Ayyar, Nicolas W. Cortes-Penfield, Kei Haga, Frederick H. Neill, Antone R. Opekun, James R. Broughman, Xi Lei Zeng, Sarah E. Blutt, Sue E. Crawford, Sasirekha Ramani, David Y. Graham, Robert L. Atmar

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations

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.

Original languageEnglish (US)
Article number638
JournalViruses
Volume11
Issue number7
DOIs
StatePublished - Jul 2019
Externally publishedYes

Keywords

  • Human norovirus cultivation
  • Intestinal enteroids/organoids
  • Virus neutralization and inactivation

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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