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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection
Rina Hashimoto1,2, Yukio Watanabe1, Abeer Keshta1
1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Insights
Human respiratory organoids offer a better model for studying respiratory syncytial virus (RSV) infection than traditional cell cultures. This advanced model accurately reflects RSV pathophysiology and aids in evaluating potential treatments.
Area of Science:
- Virology
- Stem Cell Biology
- Respiratory Medicine
Background:
- Respiratory syncytial virus (RSV) causes significant disease in young children, but its pathophysiology is poorly understood.
- Current cell models, like HEp-2, do not fully replicate the human respiratory system's response to RSV.
- Advanced models are crucial for effective RSV research and therapeutic development.
Purpose of the Study:
- To evaluate human-induced pluripotent stem cell-derived respiratory organoids as a model for RSV infection.
- To assess the utility of these organoids in pharmaceutical research for RSV.
- To compare organoid response to RSV with existing cell culture models.
Main Methods:
- Human-induced pluripotent stem cell-derived respiratory organoids were infected with RSV.
- Viral genome and protein expression, tissue damage, and cytokine levels were analyzed.
- The efficacy of monoclonal antibodies and ribavirin against RSV in organoids was tested.
Main Results:
- RSV-infected organoids showed high viral replication, epithelial damage, and increased collagen.
- Pro-inflammatory cytokine levels elevated post-RSV infection in organoids.
- Monoclonal antibodies effectively inhibited RSV infection, while ribavirin had limited impact.
Conclusions:
- Respiratory organoids provide a more accurate model for studying RSV infection and human host response.
- These organoids are valuable tools for pharmaceutical research and the development of RSV therapeutics.
- The findings support the use of organoids for advancing RSV understanding and treatment strategies.
Abstract:
Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. Whereas HEp-2 cells are widely used because of their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human-induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), although ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
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