Fig. 4.
ZIKV triggers brain inflammation and microgliosis in adult mice. Adult mice received an i.c.v. infusion of 105 PFU ZIKV, UV-inactivated ZIKV or mock medium. a Brains were processed for determination of the expression of IL-1β (a F(2,38) = 4.878, *p <0.0001, ZIKV-infected vs mock-infused mice at 6dpi, two-way ANOVA followed by Bonferroni; N = 8 (1 dpi), 6 (6 dpi), and 3 (30 dpi) (mock); 5 (1 and 6 dpi) and 3 (60 dpi) (inactivated-ZIKV); and 8 (1 dpi), 6 (6 dpi) and 3 (30 dpi) (ZIKV)mice) or TNF-α (b F(2,37) = 13.62, *p < 0.0001, ZIKV-infected vs mock-infused mice at 6 dpi; two-way ANOVA followed by Bonferroni; N = 5 (1 dpi), 7 (6 dpi) and 6 (30 dpi)(mock); 5 (1 dpi), 4 (6 dpi), and 2 (60 dpi) (inactivated-ZIKV) and 8 (1 dpi), 6 (6 dpi) and 3 (60 dpi) (ZIKV)mice. c Integrated Iba-1 immunoreactivities (optical density) in the hippocampi of ZIKV-infected mice at 6, 30, or 60 dpi (F(2,10) = 0.2612, 6 dpi: *p = 0.0110, 30 dpi: #p = 0.0554; two-way ANOVA followed by Bonferroni compared to mock-infused mice at the same time point; N = 3 (mock) and 4 (ZIKV) mice at 7 dpi; 4 mice/group at 30 dpi and 5 (mock) and 4 (ZIKV) mice at 60 dpi). d Iba-1 positive cells in the hippocampi of mice at 6 dpi (t = 4.507; *p = 0.0028; Student’s t-test; N = 5 (mock)and 4 (ZIKV) mice). e Maximum-minimum Feret index in microglia in hippocampi of mock-infused or ZIKV-infected mice at 6dpi (t = 5.205; *p = 0.002; N = 4 mice/group). f, g Representative images of Iba-1 immunoreactivity in the hippocampi of mock-infused (f) or ZIKV-infected (g) mice at 6dpi. Scale bar = 300 μm. h, i Higher magnification images of the regions defined by dashed white rectangles in panels f and g, respectively. Scale bar = 50 μm. j Representative images illustrating perivascular cuffings (top) and microglial nodules (bottom) in hippocampi of ZIKV-infused mice at 6 dpi. Scale bar = 20 μm. k–n Representative images of TEMEM119 immunolabeling in hippocampal CA1 region (k, l) and in DG (m, n) of mock-infused or ZIKV-infected mice at 6dpi. Scale bar = 50 μm. o Integrated TMEM119 immunoreactivities (optical densities) in the hippocampi of mice at 6 dpi (t(1,5) = 2.435; #p = 0.059, Student’s t-test); N = 3 (mock) and 4 (ZIKV) mice. Bars represent means ± SEM. Symbols correspond to individual mice. p–r Representative dot plot (p) and frequency of quiescent microglia (CD11b+CD45int cells; q, and activated myeloid cells (CD11b+CD45high cells; r in brains of mock- or ZIKV-infused mice at 6 dpi (q N = 6 (mock) and 4 (ZIKV) mice; r t = 14.03; *p < 0.0001; Student’s t-test; N = 6 (mock) and 4 (ZIKV) mice). s–u Representative dot plot (s) and frequencies of CD4 (t) and CD8-positive (u) cells in brains of mock- or ZIKV-infused mice at 6 dpi (t t = 3.072; *p = 0.0133; u t = 2.242; #p = 0.0517; N = 6 (mock) and 5 (ZIKV) mice; Student’s t-test). Bars represent means ± SEM; Symbols represent individual mice (a–o) or a pool of two mice (p–u). Source data from panels a–e, o, q, r, t, u are provided as Source Data File