Spatial transcriptomics uncovers vasculature-centered cellular interactions driving Japanese encephalitis progression...

Area of Science:

• Neurovirology
• Immunology
• Systems biology

Background:

• Neuropathology mechanisms of neuroinvasive viruses are not fully understood.
• Japanese encephalitis virus (JEV) is a significant cause of viral encephalitis globally.

Purpose of the Study:

• To elucidate the cellular interactions driving Japanese encephalitis (JE) pathogenesis.
• To create a spatiotemporal atlas of JE using advanced transcriptomic technology.

Main Methods:

• Infection of BALB/c mice with JEV.
• Application of Stereo-seq for in situ host and viral transcriptome analysis.
• Construction of a comprehensive spatiotemporal atlas of JE pathogenesis.

Main Results:

• Ly6c2+ monocytes identified as primary JEV carriers, abundant immune infiltrates, and IFN-γ sources in the brain.
• Ackr1+ endothelial cell activation linked to blood-brain barrier disruption and monocyte recruitment.
• Crosstalk between monocytes and endothelial cells orchestrates inflammation and cell death (pyroptosis, necroptosis).

Conclusions:

• Targeting Ly6c2+ monocyte and Ackr1+ endothelial cell interactions may mitigate JE progression.
• The study provides a framework for investigating other neurotropic viral diseases.
• Understanding cellular crosstalk is key to combating neuroinvasive viral infections.