Supporting data for "Organoid-based Investigations of Human Respiratory Viruses and Virus-host Interaction: Rhinovirus C and SARS-CoV-2"

A comprehensive understanding of respiratory viruses requires a robust and physiologically relevant in vitro system. We have established human respiratory organoids derived from adult stem cells from primary lung tissues or the epithelial cells procured from the nasal cavity. These organoids can be long-term expanded and be induced to differentiate into mature organoids. The differentiated organoids can faithfully recapitulate the genetic and functional characteristics of native respiratory epithelia, including susceptibility and host response to respiratory viruses. Using respiratory organoids, we were able to successfully propagate rhinovirus C (RV-C), a common respiratory pathogen that is typically refractory to infection in standard cell lines and gained key insights into RV-C biology and virus-host interactions. Furthermore, we leveraged the organoids to evaluate the replicative fitness of the SARS-CoV-2 Omicron BA.5 subvariant and found that BA.5 exhibited dramatically increased replicative capacity and infectivity compared to earlier variants, which was accompanied by prominent syncytium formation in the respiratory organoids. The physiologically relevant respiratory organoid system has shown great potential as a transformative tool to advance virological research and therapeutic innovation.

对呼吸道病毒的综合理解 necessitates 一个坚实且生理上相关的体外系统。我们已成功构建由初级肺组织中的成年干细胞或从鼻腔获取的上皮细胞衍生出的人呼吸道类器官。这些类器官可以长期扩增，并能诱导分化为成熟的类器官。分化的类器官能够忠实重现原位呼吸道上皮的遗传和功能特性，包括对呼吸道病毒的易感性和宿主反应。利用呼吸道类器官，我们成功繁殖了鼻病毒C（RV-C），这是一种常见的呼吸道病原体，通常对标准细胞系的感染具有抵抗力，并获得了关于RV-C生物学和病毒-宿主相互作用的宝贵见解。此外，我们利用类器官评估了SARS-CoV-2奥密克戎BA.5亚变种的复制适应性，发现BA.5相较于早期变种表现出显著增强的复制能力和传染性，这在呼吸道类器官中伴随显著的合胞体形成。这一与生理学相关的呼吸道类器官系统显示出作为推动病毒学研究与治疗创新变革性工具的巨大潜力。