Organoids: physiologically relevant ex vivo models for viral disease research

Viral diseases pose serious threats to human health, resulting in substantial economic losses. However, traditional disease models often fail to capture the full complexity of viral pathogenesis. Pluripotent and tissue stem cell-derived organoids help bridge this gap by closely mimicking the structure and function of native organs, thereby enabling new breakthroughs in studying viral pathogenesis. This review discusses the diverse applications of organoid models in virology, including infection modeling, host-virus interaction studies, CRISPR/Cas9-based gene editing, antiviral drug screening, and vaccine development. Here, we focus on human organoid models used to investigate viral infections, covering systemic viral infections (exemplified by viruses such as SARS-CoV-2, Zika virus, influenza virus, and monkeypox virus) as well as localized viral infections (exemplified by viruses including respiratory syncytial virus, herpes simplex virus 1, rotavirus, norovirus, hepatobiliary viruses, and cytomegalovirus). By advancing mechanistic insights and accelerating therapeutic discovery, organoid technology shows significant potential as a complementary tool for combating viral diseases.