ArticleInfectious medicine2026
Japanese encephalitis virus reprograms host pyrimidine metabolism to facilitate viral replication.
Article in Infectious medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pyrimidine metabolism is crucial for the replication of viruses and the functionality of host cells. However, the cell-type-specific organization of this metabolism in the central nervous system and its dysregulation during Japanese encephalitis virus (JEV) infection remain poorly understood. Here, we aimed to characterize the cell-type-specific landscape of pyrimidine metabolism in the CNS and uncover pyrimidine metabolic reprogramming during JEV infection. Methods: Single-cell RNA sequencing data from normal and JEV-infected mouse brains were analyzed to profile the expression of pyrimidine metabolic genes across neuronal, glial, and vascular cell types. Functional validation of these metabolic pathways on JEV replication was performed in Neuro-2a cells and primary mouse brain-derived mixed neuron/glia cultures using pharmacological inhibitors, metabolite supplementation, and virological assays, including quantitative reverse transcription polymerase chain reaction, immunoblotting, and plaque assay. Results: We defined a universal core program for pyrimidine homeostasis alongside specialized, function-oriented metabolic programs across neurons, glia, and vascular cells in the normal mouse brain. JEV infection triggered cell-intrinsic reprogramming of this metabolic network, with viral replication critically depending on the Conclusions: JEV rewires host brain pyrimidine metabolism in a cell-type-specific manner, revealing distinct metabolic dependencies on
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