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Title: Human iPS cell–derived respiratory organoids as a model for respiratory syncytial virus infection
Authors: Hashimoto, Rina
Watanabe, Yukio
Keshta, Abeer
Sugiyama, Masaya
Kitai, Yuki
Hirabayashi, Ai
Yasuhara, Naoko
Morimoto, Shiho
Sakamoto, Ayaka
Matsumura, Yasufumi
Nishimura, Hidekazu
Noda, Takeshi
Yamamoto, Takuya
Nagao, Miki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-8886-6145 (unconfirmed)
Takeda, Makoto
Takayama, Kazuo
Issue Date: Jul-2025
Publisher: Life Science Alliance, LLC
Journal title: Life science alliance
Volume: 8
Issue: 7
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.
Rights: This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/294607
DOI(Published Version): 10.26508/lsa.202402837
PubMed ID: 40262853
Appears in Collections:Journal Articles

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