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Advances in understanding interferon-mediated immune responses to enteric viruses in intestinal organoids

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.943334

Keywords

enteric virus; interferon; interferon-stimulated genes; norovirus; astrovirus; rotavirus; organoid; enteroid

Categories

Funding

  1. National Institutes of Health (NIH) [F32DK130248]
  2. NIH [R01 AI127552, R01 AI139314, R01 AI141478]
  3. Pew Biomedical Scholars Program of the Pew Charitable Trusts
  4. Mathers Foundation
  5. Burroughs Wellcome Fund

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This article describes the use of human intestinal enteroids (HIEs) to study the mechanisms of human enteric viral infections in vitro, as well as the role of interferons in antiviral immune responses. These research findings help to reveal important aspects of enteric viral infections and facilitate the development of treatments and vaccines.
Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses in vitro, particularly human norovirus. Accordingly, advancements in the development of antiviral therapies and vaccine strategies for enteric viral infections have been similarly constrained. Currently emerging is the use of human intestinal enteroids (HIEs) to investigate mechanisms of human enteric viral pathogenesis. HIEs provide a unique opportunity to investigate host-virus interactions using an in vitro system that recapitulates the cellular complexity of the in vivo gastrointestinal epithelium. This approach permits the exploration of intestinal epithelial cell interactions with enteric viruses as well as the innate immune responses mediated by IFNs and IFN-stimulated genes. Here, we describe recent findings related to the production, signaling, and function of IFNs in the response to enteric viral infections, which will ultimately help to reveal important aspects of pathogenesis and facilitate the future development of therapeutics and vaccines.

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