Fig. 3

Following i.c. infection, WT and Rag1^−/− mice but not Ifnar1^−/− mice develop encephalitis. a, f, k, p H&E-stained section from the CNS of sham-injected WT mice and mice infected with ZIKV at peak disease. a No inflammatory infiltrates were seen in sham-injected mice. The CNS of ZIKV-infected WT mice at day 6 post infection showed pronounced encephalitis with perivascular cuffing (f) that was less extensive in Rag1^−/− mice at day 8 post infection (p). By contrast, Ifnar1^−/− mice (k) showed only few infiltrating leukocytes, predominantly PMNs (inset, arrowheads) at peak disease (day 4 post infection). b, d, g, i, l, n, q, s Immunohistochemistry for the microglia marker Iba1. Compared with sham-injected WT mice (b), the CNS of diseased WT (g) and Rag1^−/− mice (q) revealed an increased staining intensity for Iba1 and microglia had short and thickened process characteristics for activation. Further, monocytes/macrophages formed perivascular cuffs in diseased WT (i) and Rag1^−/− mice (s). The brains from infected Ifnar1^−/− mice (l, n) showed no gross differences compared to sham controls (b, d). c, h, m, r Immunohistochemistry for the astrocyte marker GFAP. Compared with sham-injected WT mice (c), moderate astrogliosis was observed in the CNS of all infected mice independent of the genotype. e, j, o, t Immunohistochemistry for the T cell marker CD3. No T cells were seen in sham-injected mice (e), whereas diseased WT mice showed large numbers of CD3⁺ T cells in the perivascular space and diffusely infiltrating the parenchyma (j). Some CD3⁺ T cells were seen in diseased Ifnar1^−/− mice (o). Expectedly, a stain for CD3 was negative in diseased Rag1^−/− mice (t). a, b, c, f, g, h, k, l, m, p, q, r: scale bar = 50 μm; d, e, i, j, n, o, s, t: scale bar = 20 μm