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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: Zika virus vertical transmission in interferon receptor1-antagonized Rag1−/− mice results in postnatal brain abnormalities and clinical disease

Fig. 7

Prolonged ZIKV infection in AIRlow mice results in sustained CNS structural abnormalities and glial activation leading to eventual clinical neurologic disease. a Neonates born to AIRlow (blue line) and IgR (black line) treated, ZIKV infected, pregnant mice (see Results for specific mouse numbers) were followed for survival out to P14 and the results are presented as Kaplan–Meier survival curves. Each curve indicates the survival of neonates from multiple dams treated with the indicated anti-IFNAR1/normal mouse IgG dose(s) and ZIKV infectious dose. The dash-dot line plotted on the Y-axis indicates median survival as determined by Kaplan–Meier. ****p < 0.0001 indicate a significant decrease in survival based on a Log-rank Mantel-Cox curve comparison test where the AIRlow curve was compared to the IgR. b P14 naïve, IgR and AIRlow pups were evaluated for ZIKV RNA by qRT-PCR with virus-specific primers. The dotted line in (b) indicates the limit of detection for the assay. Morphometric measurements from each hemisphere of 3 naïve, 10 IgR and 3 AIRlow mice that survived to P14 are shown for (c) cerebellar area and (d) cortical thickness. Each symbol represents the mean of 3 measured sections from each hemisphere of each animal. The mean of the individually plotted data points for each group is represented by the horizontal black bars. A One-way ANOVA was used to compare cerebellar area (c, F2, 28 = 9.64, p = 0.0007) and cortical thickness (d, F2, 28 = 1.384, p = 0.2673) from samples from each group and a Tukey Multiple Comparisons Test was used to determine significance between groups. **p < 0.01, ***p < 0.001, indicate significance between groups. n.s. = not significant. Representative H&E-stained sections from P14 AIRlow (e) cerebellum and (f) spinal cord demonstrate degenerating cerebellar neurons (e, black arrows) and axonal degeneration (f, black arrows). The scale bar in (f) applies to (e). Representative cerebellar sections from (g) IgR and (h) AIRlow pups demonstrating ZIKV NS5 (green) and Iba1 (magenta) immunofluorescence labeling. The scale bar in (h) applies to (g)

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