Gastrointestinal organoids in the study of viral infections

Viruses are among the most prevalent enteric pathogens. Although virologists historically relied on cell lines and animal models, human intestinal organoids (HIOs) continue to grow in popularity. HIOs are nontransformed, 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, 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 antiviral therapeutics. Finally, we discuss the current limitations of HIOs and future directions to overcome these.