What is it about?
Japanese encephalitis virus (JEV), a mosquito-borne virus, can invade the brain and cause encephalitis. In this study, using a mouse infection model, we investigated what actually happens in the brain during the early stages of infection — from the virus infects the skin to when it first enters and begins to replicate in the brain. By applying spatial transcriptomic analysis to brain tissue sections, we revealed how the virus spreads and how the host responds at these early stages.
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Why is it important?
The findings reveal that JEV infection begins with subtle, spatially organized immune reactions in the brain long before severe inflammation develops. Glial cells near brain microvessels, including oligodendrocyte precursor cells, were identified as key early targets and mediators of antiviral responses. Distinct region- and cell-type–specific antiviral responses appeared even before JEV entered the brain. Following these antiviral responses, endothelial tight junction genes were broadly downregulated, suggesting subsequent compromise of the blood–brain barrier (BBB) integrity. These findings highlight the early involvement of glial cells in shaping brain immunity and provide new insights into JEV pathogenesis and early intervention strategies.
Perspectives
To understand how JEV crosses the blood–brain barrier, it is essential to capture the event as it occurs in vivo. Xenium in situ analysis of brain tissue soon after viral entry offers a way to approach this question.
Yasuko Orba
Hokkaido Daigaku
Read the Original
This page is a summary of: Spatial gene expression analysis reveals pathological niches in Japanese encephalitis virus neuroinvasion, Proceedings of the National Academy of Sciences, October 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2515006122.
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