ZIKV-infected monocytes promote viral dissemination and tissue damage to cerebral organoids. a, b Cerebral organoids of 3 or 5 weeks post differentiation (wpd) were cocultured with ZIKV-infected monocytes, noninfected monocytes, cell-free ZIKV, or mock for 2 days. The organoids were then fixed and processed for a immunofluorescence or b flow cytometry. a A slice and the 3D view of the same organoid are shown, which was cocultured with ZIKV-infected monocytes. The crop shows infected cells (not monocytes) in yellow. Scale bar: 50 µm. b The bar graphs represent the mean of an experiment performed in duplicate ± SD with monocytes from two donors. c–e Organotypic cultures of mouse cerebellar slices were cultured in the presence or absence of cell-free ZIKV or ZIKV-infected monocytes ± ZCL278. c Experimental design. d A staining with an anti-calbindin antibody (green) and Dapi (blue) was done to observe the tissue cytoarchitecture. Scale bar: 500 µm. e The cytoarchitecture index is a measurement of the degree of tissue injury. Three categories were defined: healthy (part of the lobule with a regular alignment of Purkinje), intermediate (partially damaged, sparse Purkinje), or altered (absence of Purkinje, impaired on the slice). For each condition, the length of the healthy, intermediate, or altered regions was measured by using ImageJ and the proportion of each category was plotted. The condition in which cerebellar slices were incubated with ZIKV-infected monocytes is the only one that significantly differed from the others. Two-tailed p value < 0.05 (*). Statistical significance was determined by using a t test. NI noninfected. Source data in b, e are provided as a Source Data file
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