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A microengineered 3D human neurovascular unit model to probe the neuropathogenesis of herpes simplex encephalitis

Author

Listed:
  • Min Zhang

    (Chinese Academy of Sciences)

  • Peng Wang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Yunsong Wu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lin Jin

    (Shanxi Agricultural University)

  • Jiayue Liu

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Pengwei Deng

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Rongcan Luo

    (Chinese Academy of Sciences)

  • Xiyue Chen

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mengqian Zhao

    (Chinese Academy of Sciences)

  • Xu Zhang

    (Chinese Academy of Sciences)

  • Yaqiong Guo

    (Chinese Academy of Sciences)

  • Ying Yan

    (Guizhou Medical University)

  • Yingtong Di

    (Chinese Academy of Sciences)

  • Jianhua Qin

    (Chinese Academy of Sciences
    University of Science and Technology of China
    University of Science and Technology of China
    University of Chinese Academy of Sciences)

Abstract

Herpes simplex encephalitis (HSE) caused by HSV-1 is the most common non-epidemic viral encephalitis, and the neuropathogenesis of HSE remains elusive. This work describes a 3D human neurovascular unit (NVU) model that allows to explore the neuropathogenesis of HSE in vitro. This model is established by co-culturing human microvascular endothelial cells, astrocytes, microglia and neurons on a multi-compartment chip. Upon HSV-1 infection, this NVU model exhibited HSE-associated pathological changes, including cytopathic effects, blood-brain barrier dysfunction and pro-inflammatory cytokines release. Besides, significant innate immune responses were observed with the infiltration of peripheral immune cells and microglial activation. Transcriptomic analysis revealed broadly inflammatory and chemotactic responses in host cells. Mechanistically, we found HSV-1 could induce severe suppression of autophagic flux in glial cells, especially in microglia. Autophagy activators could effectively inhibit HSV-1 replication and rescue neurovascular injuries, indicating the utility of this unique platform for studying neurological diseases and new therapeutics.

Suggested Citation

  • Min Zhang & Peng Wang & Yunsong Wu & Lin Jin & Jiayue Liu & Pengwei Deng & Rongcan Luo & Xiyue Chen & Mengqian Zhao & Xu Zhang & Yaqiong Guo & Ying Yan & Yingtong Di & Jianhua Qin, 2025. "A microengineered 3D human neurovascular unit model to probe the neuropathogenesis of herpes simplex encephalitis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59042-4
    DOI: 10.1038/s41467-025-59042-4
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