SUMMARY Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells, and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components. Functionally, ZIKV-NS2A, but not DENV-NS2A, destabilizes the AJ complex, resulting in impaired AJ formation and aberrant radial glial fiber scaffolding in the embryonic mouse cortex. Similarly, ZIKA-NS2A, but not DENV-NS2A, reduces radial glial cell proliferation and causes AJ deficits in human forebrain organoids. Together, our results reveal pathogenic mechanisms underlying ZIKV infection in the developing mammalian brain.

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Four doses (equivalent to 4, 2, 1, and 0.5 liter water) of organic extracts from raw, treated and drinking waters sampled from seven different treatment plants in five cities in Korea were challenged to the Ames test using S. typhimurium strains TA98 and TA100 in the presence/absence of S9 mix. The mutagenicity was usually observed from chlorine-treated (28.6%) and drinking (42.9%) waters rather than raw (3.4%) waters. The strain TA98 (33.3%) was more sensitive to detect the mutagenicity of water samples than the strain TA100 (16.7%). However, the absence of S9 mix showed higher mutagenic activity of waters compared to the presence of S9 mix, corresponding to the detection of 42.9% and 7.1%, respectively. These results indicate that the bacterial mutagenicity of treated and drinking waters may be derived from chlorination in water treatment plants but that the mutagenicity in humans may be limited due to enzymatic metabolism.