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.