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

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 and Jianhua Qin ()
Additional contact information
Min Zhang: Chinese Academy of Sciences
Peng Wang: University of Science and Technology of China
Yunsong Wu: Chinese Academy of Sciences
Lin Jin: Shanxi Agricultural University
Jiayue Liu: University of Science and Technology of China
Pengwei Deng: University of Science and Technology of China
Rongcan Luo: Chinese Academy of Sciences
Xiyue Chen: 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

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59042-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59042-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59042-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().