Recent Advances in Nose and Lung Organoid Models for Respiratory Viral Research

Studies on human respiratory viral infections and pathogenesis have historically been conducted using immortalized cells and animal models. However, these models are limited in their ability to recapitulate the complex structure of the human airway or the full spectrum of disease symptoms observed in humans. Recently, nose and lung organoids have revolutionized culture complexity in infection biology and have demonstrated potential for research on respiratory virus infections in humans. In this opinion, we review how advances in human nose and lung organoid models, which are able to express all cell types of the respiratory epithelia, i.e., Club, basal, goblet, and ciliated cells, have provided novel insight into the pathogenesis, age-dependent susceptibility, viral attenuation signature, and immune mechanisms of respiratory viruses such as SARS-CoV-2, respiratory syncytial virus, and influenza virus. The models have also demonstrated potential for studying hitherto uncultivable human viruses and to be useful for studies of zoonotic risk.