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Review
. 2021 May 27;13(6):999.
doi: 10.3390/v13060999.

Organoids to Dissect Gastrointestinal Virus-Host Interactions: What Have We Learned?

Sue E Crawford  1 , Sasirekha Ramani  1 , Sarah E Blutt  1 , Mary K Estes  1   2
Affiliations
Review

Organoids to Dissect Gastrointestinal Virus-Host Interactions: What Have We Learned?

Sue E Crawford et al. Viruses. .

Abstract

Historically, knowledge of human host-enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host-microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.

Keywords: Transwell®; diarrhea; enteric virus; enteroid; gastrointestinal infection; host–virus interactions; human intestinal organoid.

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Conflict of interest statement

The authors declare that no competing interests exist.

Figures

Figure 1
Figure 1
Human intestinal organoids. (a) Generation of HIOs from stem cells isolated from intestinal biopsies or tissue. (b) HIOs can be cultured as 3D HIOs in extracellular matrices such as Matrigel® or plated, either as 2D cultures on 96 well plates or as polarized monolayers on Transwells®. HIOs can be plated on either on Matrigel®- or collagen-coated surfaces. In each of these formats, HIOs can be used as undifferentiated or differentiated 3D or 2D cultures. The apical and basolateral surfaces can be accessed by pathogens on Transwells®, while the apical surface of 3D HIOs is accessed by mechanical disruption. Created with BioRender.com (accessed on 26 May 2021).
Figure 2
Figure 2
Expression of genes involved in innate immunity and immune modulation following infection of differentiated human intestinal organoids with SARS-CoV-2 coronavirus. Genes are listed on the left, and infection conditions are listed at the top. From [34].
Figure 3
Figure 3
Overview of what we have learned from virus–HIO studies. Future areas of research are listed in green. Created with BioRender.com (accessed on 26 May 2021).
See this image and copyright information in PMC

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