Modeling respiratory viral infections actual in the first quarter of the XXI century: from primary epithelial cultures to organoids

Respiratory viral infections pose a serious public health issue resulting in high morbidity and mortality, as well as profound socioeconomic losses. Therefore, it accounts for a need to research respiratory viral infections immunopathogenesis, development of effective vaccines and antiviral drugs, as well as measures to monitor viral infections. The aim of the review is to analyze current methods for modeling respiratory viral infections ex vivo. Material and methods. There were analyzed current data regarding development and application of models based on primary epithelial cells (PECs) derived from various anatomical sites of the human respiratory tract (RT) and 3D cell cultures. For this, there were assessed 158 publications retrieved from the main databases (Web of Science, PubMed, Scopus, Elsevier, Google Scholar and RSCI until January 2025) by querying the keywords: respiratory viruses; primary airway epithelium cultures; organoids; immunopathogenesis; tropism; cellular receptors; cytokines. Results and discussion. The analysis showed that models based on PECC are widely used in virological studies of respiratory viral infections, which, however, is coupled to certain disadvantages. More advanced are RT 3D models (organoids or mini-organs, spheroids, “organs on a chip”), which allow not only to reproduce infectious processes, but also to study immunopathogenesis taking into account the immunometabolic and immunoneurological status. Using RT PECs and 3D models, the properties of a number of respiratory viruses actual in the first quarter of the XXI century (influenza and parainfluenza, pneumoviruses, coronaviruses, rhinoviruses, bocaviruses, adenoviruses) such as tissue tropism, receptor interactions and innate immune response were assessed. Moreover, we also present information on promising models for respiratory viral infections that reproduce essential aspects of RT physiology. Conclusion. The primary biotechnological aim for virological studies of respiratory viral infections is to generate a multiparameter, reproducible and cost-effective RT modeling system that imitates its morphological and functional structure.