Human airway organoids as a versatile model to study BSL-4 virus replication and pathogenesis

TL;DR

Human airway organoids can be used to study dangerous BSL-4 viruses like Ebola in a safe and effective way.

Contribution

Airway organoids provide a standardized human tissue model for BSL-4 virus research that is more translatable to human disease.

Findings

Airway organoids replicate BSL-4 viruses effectively and mirror the cell composition of whole lung tissue.

Organoids derived from nasal swabs offer a versatile 3D model for studying virus-host interactions and antiviral testing.

The model allows research on infection kinetics and immune evasion in a controlled environment.

Abstract

Research with BSL-4 viruses such as Ebola, Marburg, and Nipah presents significant challenges due to their high virulence and the stringent containment measures required. This study establishes human airway organoids as a robust model for investigating BSL-4 pathogens. In contrast to conventional cell lines, airway organoids enable investigation of virus-host interactions within a human tissue context, providing insights that are more directly translatable to human disease. We generated airway organoids from both clinical donor tissues and commercially available nasal epithelial cells and showed in comparative analyses with whole lung tissue that these organoids are comparable in terms of cell composition. Despite biological variations, airway organoids derived from different sources and donors exhibit a remarkably similar cellular make-up. We further demonstrated that organoids derived from nasal swabs can effectively replicate BSL-4 viruses. This establishes them as a standardized 3D model for broader research applications including infection kinetics, immune evasion, and tissue-specific tropism within a controlled environment. This platform provides a powerful tool for antiviral testing and studying virus-host interactions, thus helping bridge critical gaps in high containment virus research and advancing our understanding of these pathogens, bypassing some of the challenges of animal models.

The online version contains supplementary material available at 10.1038/s41598-026-45813-6.

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