Fig. 2 |. ZiKV induces neuroinflammation and neuronal loss in the hippocampus.

a-d, ZIKV and WNV induce differential neuropathology in the hippocampus of WT mice. IHC analysis revealed that the number of microglia (IBA1⁺), astrocytes (GFAP⁺), and T cells (CD3⁺) increases in the hippocampus after infection with either virus, but the number of neurons (NeuN⁺) decreases following ZIKV infection. a,b, Representative images shown. Scale bars, 20 μm. c,d, The number of cells were quantified as indicated. For c, n = 3 (0 d.p.i.) or 5 (7, 25 d.p.i.) mice per group. IBA1, P = 0.0051 (0 versus 7d.p.i.) and P= 0.0001 (0 versus 25d.p.i.); GFAP, P = 0.0086 (0 versus 7d.p.i.) and P = 0.0008 (0 versus 25 d.p.i.); CD3, P = 0.0001 (0 versus 25 d.p.i.); NeuN, P = 0.0342 (0 versus 7d.p.i.) and P= 0.0046 (0 versus 25 d.p.i.). For d, n = 3 (0,25) or 4 (7d.p.i.) mice per group. IBA1, P = 0.0125; CD3, P = 0.0367. e-h, T cells persist in the hippocampus after viral clearance, and microglia demonstrate persistent activation. Flow cytometry analysis of cells isolated from the hippocampus of CC3CR1^GFPCCR2^RFP reporter animals at the indicated d.p.i. (gating strategy shown in Supplementary Fig 2). Data are representative of two independent experiments. e,f, ZIKV (e) and WNV (f) infection leads to increased expression of CD103 in CD45^hiCD11b⁻CD8⁺ T cells (n = 3 mice per group; P<0.0001). g,h, CD45^midCD11b⁺Cx3CR1⁺CCR2⁻ microglia isolated from the hippocampus of ZIKV-infected (g) and WNV-infected mice (h) express high levels of MHCII at 25 d.p.i. (n = 3 mice per group; P= 0.0035 (g) and P = 0.0023 (h)). For c-h, data represent the mean±s.d. and were analyzed by two-way ANOVA, corrected for multiple comparisons (c and d) or by unpaired two-sided t-test (e-h). *P<0.05, **P< 0.005, ***P< 0.001, ****P< 0.0001