Fig. 4

2-DG and DCA alleviate neuroinflammation in a mouse model of WNV infection. A Experimental design and sample collection. Mice were intraperitoneally infected with 10⁴ PFU of WNV and treated with the glycolysis inhibitors 2-DG (500 mg/kg) or DCA (200 mg/kg) diluted in saline serum by intraperitoneal injection once daily (QD) for 7 days, starting on day 0 after infection. Control mice were treated with saline serum. Animals were humanely euthanized at 7 days after infection (n = 5). Figure was created with BioRender. B WNV viral burden in the brain. Virus load was quantified in the brain by RT-qPCR. C Assessment of immune cell activation and infiltration in the brain of WNV-infected mice by using bulk RNA-seq expression data to estimate the abundance of cell types during the progress of WNV neuroinvasion with CellKb tool (n = 5 for 2-DG and DCA and n = 3 for vehicle). D, E Effect of the treatment with 2-DG or DCA on the DEGs related to the antiviral mechanism by IFN-stimulated genes (D) and signaling by interleukins (E) in the brain of infected animals (n = 5 for 2-DG and DCA and n = 3 for vehicle). F–I Cytokine induction in the brain of infected mice assessed by RT-qPCR: E Ccl2; F Cxcl10; G Cxcl11; H Tnf-α. *p < 0.05; **p < 0.01; for Kruskal–Wallis test and Dunn’s correction for multiple comparisons (F, H, I) or one-way ANOVA and Dunnett’s correction for multiple comparison (G) (n = 5)