Human respiratory organoids have opened up new avenues for studying human rhinovirus C (HRV-C), a prevalent pathogen responsible for upper respiratory infections. Unlike its relatives, HRV-C has been resistant to propagation using traditional cell culture techniques, presenting significant obstacles for researchers. A groundbreaking study demonstrates the potential of human respiratory organoids to not only cultivate HRV-C but also elucidate complex virus-host interactions.
Researchers from the University of Hong Kong have developed organoid-based systems to propagate HRV-C successfully. These organoids mimic human airway and nasal epithelial cells closely, facilitating the virus's replication under controlled conditions. The study's findings highlight the comparative susceptibility of different organoid types, with nasal organoids showing greater vulnerability to HRV-C than airway organoids.
HRV-C is known for being linked with acute respiratory infections and exacerbations of chronic respiratory diseases. Despite its prevalence, the inability to culture HRV-C has posed challenges for comprehending its biology and developing therapeutic strategies. By employing innovative organoid technology derived from adult stem cells, the researchers have established systems capable of sustaining serial HRV-C passage.
During the study, airway organoids were treated with CYT387—an immunosuppressive medication—to allow for effective virus propagation. The data revealed a notable difference between the immune responses observed: airway organoids exhibited more substantial antiviral reactions compared to nasal organoids. These results suggest distinct roles for each organoid type in simulating respiratory infections.
The study emphasized the strong innate immune responses generated by airway organoids when infected with HRV-C. This immune activation may hamper viral replication, with airway organoids showing enhanced inflammation and cytokine production. Conversely, nasal organoids displayed less immune activation, which may explain their increased susceptibility to viral infection.
Another significant advancement of this research is its implication for exploring other uncultivable human and animal viruses. The organoid culture system developed could serve as a powerful tool for future virology studies beyond HRV-C, addressing the urgent need to understand many viral pathogens.
Overall, this study highlights the innovative use of human respiratory organoids to advance our knowledge of HRV-C, providing new insights relevant for future antiviral drug development and enhancing our broader comprehension of viral respiratory infections.