Abstract
Abstract
Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia, yet the host pathways that sustain its replication in the central nervous system remain poorly defined, and no antiviral therapies exist. Here we combine time-resolved transcriptomics and proteomics in mouse neuroblastoma (Neuro-2a) cells with time-resolved proteomics of infected mouse brain, integrated using directionality-penalized p-value merging. JEV infection was accompanied by progressive induction of interferon-stimulated proteins and by changes in the abundance of enzymes of central carbon and energy metabolism, spanning the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation and glutaminolysis. Temporal clustering of the brain proteome linked oxidative phosphorylation remodelling to a dependence on glutamine metabolism. Glutamine antagonism with DON reduced viral RNA, whereas glycolytic inhibition and AKT modulation did not significantly alter it under the conditions tested. Silencing of the mitochondrial transaminase GOT2 reduced JEV RNA, viral protein, and infectious virus production in human SH-SY5Y cells. Our findings identify a glutamine-GOT2 axis as a metabolic dependency of JEV and a candidate host-directed antiviral target.