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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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015132 | PMC |
http://dx.doi.org/10.26508/lsa.202402837 | DOI Listing |
Commun Biol
September 2025
The Key Laboratory of Advanced Interdisciplinary Studies, School of Public healthy, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Adenosine-to-inosine (A-to-I) RNA editing is a critical post-transcriptional modification that enhances tumor genome diversity and contributes to cancer progression. In non-small cell lung cancer (NSCLC), while specific A-to-I editing events have been identified, their functional mechanisms and clinical relevance remain poorly understood. Here, through whole-transcriptome analysis of NSCLC specimens, we discovered a hyper-editing event at position c.
View Article and Find Full Text PDFCurr Opin Virol
September 2025
Wageningen University and Research, Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, the Netherlands. Electronic address:
Development of multispecies well-differentiated airway epithelial cell (WD-AEC) models derived from either primary cells or airway organoids has led to novel options for in vitro characterization of host-pathogen interactions for viruses associated with the respiratory disease complex in livestock. Whereas assessment of adaptive immune responses to infection or vaccination currently still requires studies in animals, viral host restriction, tropism, entry, replication, virulence, and innate host responses of the respiratory epithelium can effectively be studied in WD-AEC cultures. Moreover, these models are also suitable for highly sensitive isolation of field strains of respiratory viruses that can replicate to relatively high titers without relying on multiple passages to generate adequate virus stocks with reduced risk of cell-culture adaptations compared to passaging in immortalized cell lines.
View Article and Find Full Text PDFJ Virol
August 2025
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China.
Viral diseases pose serious threats to human health, resulting in substantial economic losses. However, traditional disease models often fail to capture the full complexity of viral pathogenesis. Pluripotent and tissue stem cell-derived organoids help bridge this gap by closely mimicking the structure and function of native organs, thereby enabling new breakthroughs in studying viral pathogenesis.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
The efficacy of VIR-7831, a class 3 anti-SARS-CoV-2 monoclonal antibody (mAb), was demonstrated repeatedly in clinical trials; yet, reduced neutralization against Omicron variants in cell-line-based neutralization assays led to its withdrawal from clinical use. We developed organoid-based neutralization assays to measure mAb potency. We found that most class 3 mAbs, especially those not blocking receptor-binding domain-ACE2 binding, including VIR-7831, were substantially underestimated in cell-line-based assays.
View Article and Find Full Text PDFPLoS Pathog
August 2025
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California, United States of America.
Hantaviruses are zoonotically transmitted from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The recent discovery of interhuman-transmitted Andes virus (ANDV) necessitates the systematic identification of cell tropism, infective potential, and potent therapeutic agents. We utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses.
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