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A skin organoid-based infection platform identifies an inhibitor specific for HFMD

Author

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  • Jun Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    National Clinical Research Center for Dermatologic and Immunologic Diseases)

  • Jie Ma

    (Beijing Institute of Lifeomics)

  • Ruiyuan Cao

    (Beijing Institute of Pharmacology and Toxicology)

  • Qiyu Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    National Clinical Research Center for Dermatologic and Immunologic Diseases)

  • Mansheng Li

    (Beijing Institute of Lifeomics)

  • Wenwen Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    National Clinical Research Center for Dermatologic and Immunologic Diseases)

  • Yujie Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wei Li

    (Beijing Institute of Pharmacology and Toxicology)

  • Yunping Zhu

    (Beijing Institute of Lifeomics)

  • Ling Leng

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

The EV-A71 poses a serious threat to the health and lives of children. The EV-A71 can be transmitted by direct and indirect skin contact. Therefore, there is an urgent need to create novel skin models using human-derived cells to study the biology and pathogenesis of the virus and facilitate drug screening. Here, we use human induced pluripotent stem cells-derived skin organoids (hiPSC-SOs) as a model for EV-A71 infection and find that multiple cell types within the skin organoids, including epidermal cells, hair follicle cells, fibroblasts, and nerve cells, express EV-A71 receptors and are susceptible to EV-A71 infection. We elucidate the specific response of different cell types to EV-A71 and reveal that EV-A71 infection can degrade extracellular collagen and affect fibroblasts. We find that EV-A71 can mediate epidermal cell damage through autophagy and Integrin/Hippo-YAP/TAZ signaling pathways, thereby promoting hyperproliferation of progenitor cells. Based on this finding, we identify an autophagy-associated protein as a drug target of EV-A71 and discover an EV-A71 replication inhibitor. Altogether, these data suggest that hiPSC-SOs can be used as an infectious disease model to study skin infectious diseases, providing a valuable resource for drug screening to identify candidate virus therapeutics.

Suggested Citation

  • Jun Li & Jie Ma & Ruiyuan Cao & Qiyu Zhang & Mansheng Li & Wenwen Wang & Yujie Wang & Wei Li & Yunping Zhu & Ling Leng, 2025. "A skin organoid-based infection platform identifies an inhibitor specific for HFMD," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57610-2
    DOI: 10.1038/s41467-025-57610-2
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    References listed on IDEAS

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    1. Jiyoon Lee & Cyrus C. Rabbani & Hongyu Gao & Matthew R. Steinhart & Benjamin M. Woodruff & Zachary E. Pflum & Alexander Kim & Stefan Heller & Yunlong Liu & Taha Z. Shipchandler & Karl R. Koehler, 2020. "Hair-bearing human skin generated entirely from pluripotent stem cells," Nature, Nature, vol. 582(7812), pages 399-404, June.
    2. Abhay Kotecha & Quan Wang & Xianchi Dong & Serban L. Ilca & Marina Ondiviela & Rao Zihe & Julian Seago & Bryan Charleston & Elizabeth E. Fry & Nicola G. A. Abrescia & Timothy A. Springer & Juha T. Hui, 2017. "Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus," Nature Communications, Nature, vol. 8(1), pages 1-8, August.
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