Human iPS cell–derived respiratory organoids as a model for respiratory syncytial virus infection
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.
Authors
- Naoko Yasuhara
- Takuya Yamamoto (ORCID: https://orcid.org/0000-0002-0022-3947)
- Rina Hashimoto (ORCID: https://orcid.org/0000-0002-7174-4563)
- Yuki Kitai (ORCID: https://orcid.org/0000-0003-3271-6807)
- Miki Nagao (ORCID: https://orcid.org/0000-0002-8886-6145)
- Ayaka Sakamoto (ORCID: https://orcid.org/0000-0001-6922-1280)
- Yasufumi Matsumura (ORCID: https://orcid.org/0000-0001-8595-8944)
- Yukio Watanabe (ORCID: https://orcid.org/0000-0003-1504-4244)
- Takeshi Noda (ORCID: https://orcid.org/0000-0002-0658-4663)
- Kazuo Takayama (ORCID: https://orcid.org/0000-0002-1132-2457)
- Masaya Sugiyama (ORCID: https://orcid.org/0000-0002-9084-7197)
- Ai Hirabayashi (ORCID: https://orcid.org/0000-0002-6209-5960)
- Makoto Takeda (ORCID: https://orcid.org/0000-0002-8194-7727)
- Shiho Morimoto
- Hidekazu Nishimura (ORCID: https://orcid.org/0000-0002-5681-7971)
- Abeer Keshta
Institutions
- Kyoto University (JP)
- Japan Science and Technology Agency (JP)
- National Center for Global Health and Medicine (JP)
- Sendai Medical Center (JP)
- RIKEN Center for Advanced Intelligence Project (JP)
- Medical Research Institute (LK)
- Institute of Science Tokyo (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2025-04-22
- DOI
- https://doi.org/10.26508/lsa.202402837
- Citations
- 8
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 10.83
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science