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Fig. 2 | Acta Neuropathologica Communications

Fig. 2

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

Fig. 2

ZIKV broadly infect neurons within the CNS of P7 AIRlow neonates. P7 neonatal whole brain from naïve, IgR and AIRlow pups was evaluated for (a) ZIKV RNA by qRT-PCR with virus-specific primers. Each symbol indicates an individual brain. The mean of the individually plotted data points for each group is represented by the horizontal black bars. The dotted line in (a) indicated the limit of detection for the assay. Data was analyzed by a One-way ANOVA (F2, 20 = 12.56, p = 0.0003) with a Tukey Multiple Comparisons Test to determine significance between groups (***). Whole brain sections from b IgR and c AIRlow neonates were immunohistochemically labeled for ZIKV NS5 antigen (green) and cell nuclei (grey, Hoechst) and visualized via fluorescence microscopy. Scale bar in (c) applies to (b). Cerebellum from (d, h) naïve, (e, i) IgR and (f, j) AIRlow mice were dual chromogenic labeled for (dg) Calbindin (yellow) and ZIKV NS2B (purple) or (hk) NeuN (yellow) and ZIKV NS2B (purple) to demonstrate cellular organization and neuronal infection. The normal position and shape of the granular layer (GL), Purkinje cell layer (PCL), molecular layer (ML) and external germinal layer (EGL) are shown in a naïve mouse cerebellum labeled with (d) Calbindin and (h) NeuN at the P7 time point. Calbindin clearly labels Purkinje cell bodies in PCL (d, lower left inset) and dendrites in the ML (d, lower left inset, red arrow) and neurons associated with white matter (WM, d, lower right inset, red arrow) while NeuN labels neurons in the granular layer and maturing granular neurons as they emerge from the EGL to populate the GL. The black lines in (e, i) highlight the normal-appearing PCL and ML in an IgR mouse. These structures appear similar to those in the naïve mouse (d, h, PCL and ML). In contrast, the black lines in (f, j) highlight the diminished PCL and ML in an AIRlow mouse with the distance between each line having decreased. Likewise, notice the disorganization and sparsity of cells in the GL of IgR (i) and AIRlow (j) mice, relative to the ordered GL in the naïve mouse (h). The asterisks in (hj) highlight the maturing granular neurons that expression NeuN as they emerge from the EGL to populate the GL in a naïve, IgR and AIRlow mouse respectively. The blue boxes in (f) and (j) corresponds to the higher magnification images in (g) and (k) respectively. The black arrows in (g) and (k) demonstrate ZIKV and neuronal marker dual-labeled infected neurons, which result in red-colored cells. In contrast, cerebellar neurons that did not label with Calbindin, but are ZIKV positive are labeled purple (green arrows in g). The scale bar in (d) also applies to (e, f, h and i)

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