Fig. 2.

Cellular metabolism in the brain is altered by neurotrophic virus infection. Upon infection, there is a systemic metabolic alteration in neuron and astrocyte. The astrocyte to neuron lactate shuttle is inhibited and subsequently enhanced TCA cycle and oxidative phosphorylation in astrocytes. To fuel active TCA cycle, virus may activate fatty acid β-oxidation and glutamine metabolism. Within the neuron, the metabolic flow of glycolysis, TCA cycle, and oxidative phosphorylation is disrupted and selectively increased pentose phosphate pathway to sustain viral replication. Reduction of lactate production from astrocyte and dysregulation of neuron metabolism cooperatively induce neuron dysfunction. Abbreviation: α-KG, alpha ketoglutarate; β-Ox, beta oxidation; Gln, glutamine; Glu, glutamate; LDH, lactate dehydrogenase; NMN, nicotinamide mononucleotide; PPP, pentose phosphate pathway; OAA, oxaloacetate; OXPHOS, oxidative phosphorylation; SucCoA, succinyl-CoA; TCA, tricarboxylic acid