Put Some Guts into It: Intestinal Organoid Models to Study Viral Infection.

Inés García-Rodríguez,Dasja Pajkrt,Katja C Wolthers,Adithya Sridhar

doi:10.3390/v12111288

Abstract

The knowledge about enteric viral infection has vastly increased over the last eight years due to the development of intestinal organoids and enteroids that suppose a step forward from conventional studies using cell lines. Intestinal organoids and enteroids are three-dimensional (3D) models that closely mimic intestinal cellular heterogeneity and organization. The barrier function within these models has been adapted to facilitate viral studies. In this review, several adaptations (such as organoid-derived two-dimensional (2D) monolayers) and original intestinal 3D models are discussed. The specific advantages and applications, as well as improvements of each model are analyzed and an insight into the possible path for the field is given.

Highlights

The intestinal epithelium forms a physical barrier between the body and the external environment.This polarized barrier is composed of a single cell layer with different cell types that execute several functions including nutrient uptake and protection from pathogens, such as enteric viruses [1,2].These pathogens can alter the normal function of the epithelium in several ways such as cell death, disruption of tight junctions (TJ) between the cells, deregulation of the ion transport across the epithelium, or induction of inflammation by cytokine and chemokine responses [3].Historically, host-virus interactions have been studied using cancer-derived or immortalized cell lines
(2D) monolayers in standard culture plates, these cell lines can be grown in permeable supports, such as Transwell® inserts, where they can form a polarized monolayer with TJs and adherens junctions [4]
Despite many attempts, some viruses, such as human norovirus, cannot be cultured using standard 2D monolayer cultures, requiring alternative models for in-depth studies. One of these models is the rotating-wall vessel (RWV) bioreactors that allow the growth of three-dimensional (3D) cell spheres that can be subjected to physiological conditions of fluid-shear

Summary

Introduction

The intestinal epithelium forms a physical barrier between the body and the external environment. A turning point for in vitro enteric pathogen studies came in 2011 when a protocol for the culture to culture human norovirus for the first time [12] For this particular purpose, this model has of intestinal organoids derived from human pluripotent stem cells (PSCs) [16] was developed Vitro enteric pathogen studies came 2011 were whenstudied a protocol rotavirus clinical isolates After this first demonstration, more in viruses usingfor thisthe culture of intestinal organoids derived from human pluripotent stem cells (PSCs). Material, the most common way of generating organoids is by using embryonal or induced PSCs. Enterosphere: spherical structure composed of intestinal epithelial cells that appears as a. This observation, together with an increase in replication after detergent treatment of the epithelium, suggests that the protein may have a role in membrane disruption enhancing viral release [28]

Organoids and Organoid-Derived Models

Intestine-On-A-Chip

Conclusions and Future Perspectives