Gastrointestinal organoids in the study of viral infections

Abstract

Viruses are among the most prevalent enteric pathogens. While virologists historically relied on cell lines and animal models, human intestinal organoids (HIOs) continue to grow in popularity. HIOs are non-transformed, stem cell derived, ex vivo cell cultures that maintain the cell type diversity of the intestinal epithelium. They offer higher throughput than standard animal models while more accurately mimicking the native tissue of infection than transformed cell lines. Here, we review recent literature that highlights virological advances facilitated by HIOs. We discuss the variations and limitations of HIOs, but also how HIOs have allowed for the cultivation of previously uncultivatable viruses and how they have offered insight into tropism, entry, replication kinetics, and host-pathogen interactions. In each case, we discuss exemplary viruses and archetypal studies. We discuss how the speed and flexibility of HIO-based studies contributed to our knowledge of SARS-CoV-2 and anti-viral therapeutics. Finally, we discuss current limitations of HIOs and future directions to overcome these.

Role of the microbiota-gut-brain axis in postacute COVID syndrome

“…Intestinal epithelial cell infection leads to local inflammatory responses and subsequent impacts on the gut microbiome, which may all contribute to GI symptoms ( 47 ). Studies using human gastric and intestinal organoids were crucial early in the pandemic to study viral entry and novel antiviral therapy against SARS-CoV-2-induced disease ( 48 , 49 ). Large interindividual variability in susceptibility to infection was highly correlated to ACE2 expression levels ( 50 ).…”