Varicella-zoster virus infection of the central nervous system: clinical features and proteomic analysis of cerebrospinal fluid.

Authors

Yu Zhang, Ruohao Li, Yanbo Zhang, Lulu Zheng, Kaixuan Bai, Xuejiao Qi, Xin Chen, Yanan Zhang, Zhijiao Song, Lantao Liang, Meiling Zhang, Hui Bu

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1835634. Epub Jun 15, 2026.

Abstract

Varicella-zoster virus (VZV) involvement of the central nervous system (CNS) can cause severe complications; however, the underlying pathogenic mechanisms remain incompletely understood. This study describes the clinical characteristics of VZV CNS infection and explores the molecular mechanisms involved through cerebrospinal fluid (CSF) proteomic analysis.
This study included 69 patients diagnosed with VZV CNS infection at our center. Their clinical symptoms, laboratory tests, and neuroimaging results were analyzed. CSF samples from nine patients with VZV CNS infection (VZV group) and 10 controls without CNS infection (Ctrl group) were subjected to proteomic analysis.
The most common clinical manifestations were headache (79.7%), fever (56.5%), and motor/sensory disturbances (30.4%). Neuroimaging revealed abnormal brain parenchyma in 18.8% of the cases. CSF from most patients showed elevated white blood cell counts (0-1400 × 10⁶/L) and protein levels (0.11-7.61 g/L), and elevated cerebrospinal fluid pressure (60-330 mmH₂O). Proteomic analysis indicated the number and abundance of CSF proteins to be markedly higher in the VZV group than in the Ctrl group. Up-regulated proteins in the VZV group were primarily associated with type I interferon signaling, pyroptosis, and increased blood-brain barrier permeability. Gene Ontology enrichment analysis indicated that upregulated proteins were predominantly associated with innate antiviral immunity. Wikipathways were enriched for lymphocyte activation and inflammatory signaling pathways.
This study integrates clinical and proteomic analyses to reveal the clinical and molecular features of VZV CNS infection. Synergistic over-activation of the type I interferon response, inflammatory signaling, and lymphocyte activation drives a robust neuroinflammatory reaction, which may underlie blood-brain barrier disruption and neurological deficits. Furthermore, over-activation of the complement system in severe encephalitis provides new insights for understanding disease severity and potential therapeutic targets. These findings underscore the potential of this approach for developing diagnostic markers and targeted therapeutic strategies.

PMID:
42376316
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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