Figure 4. ZIKV infection is associated with evidence of apoptosis in the fetal brain.
Pregnant Infar1−/− dams were infected with 103 FFU of ZIKV via a subcutaneous route. Infected (left) or uninfected (right) Ifnar1+/− E13.5 fetuses were stained with the apoptotic marker activated caspase-3 (AC3; red) and the proliferative marker Ki-67 (green). Sagittal images of representative infected (A) and uninfected (E) fetal heads showing high expression of Ki-67 along brain regions adjacent to ventricles indicative of proliferating neural progenitor cells in the neuroepithelium. Lettered box regions (B-D and F-H) in these images are magnified in corresponding panels below. Higher levels of apoptosis can be seen in the midbrain (Panels B-C) and hindbrain (Panel D) of the infected Ifnar1+/− fetus. Alternatively, low levels of physiological apoptosis are seen in the absence of infection (Panels F-H). I. Diagram depicting the developing E13.5 fetal brain in sagittal view including the forebrain (green), midbrain (blue), and hindbrain (red). Images are representative of 4-5 sections per fetus from 2 fetuses.