Zika virus (ZIKV) infection leads to microcephaly in newborns. Flaviviruses are known to secrete NS1 protein extracellularly and its concentration in serum directly co-relate to disease severity. The presence of ZIKV-NS1 near the brain microvascular endothelial cells (BMVECs) affects blood-brain-barrier, which is composed of tight junctions (TJs) and adherens junctions (AJs). Viruses utilize different strategies to circumvent this barrier to enter in brain. The present study demonstrated the mechanism of junctional integrity disruption in BMVECs by ZIKV-NS1 protein exposure. The Transendothelial Electrical Resistance and sodium fluorescein migration assays revealed the endothelial barrier disruption in BMVECs exposed to ZIKV-NS1 at different time (12hr and 24hr) and doses (500 ng/mL, 1000 ng/mL and 1500 ng/mL). The exposure of ZIKV-NS1 on BMVECs led to the phosphorylation of AJs and suppression of TJs through secreted ZIKV-NS1 in a bystander fashion. The activation of NADPH dependent reactive oxygen species activity and redox sensitive tyrosine kinase further increased the phosphorylation of AJs. The reduced expression of the phosphatase led to the increased phosphorylation of the AJs. The treatment with Diphenyleneiodonium chloride rescued the phosphatase and TJs expression and suppressed the expression of kinase and AJs in BMVECs exposed to ZIKV-NS1.

寨卡病毒（ZIKV）感染导致新生儿小头畸形。黄病毒已知在细胞外分泌NS1蛋白，其在血清中的浓度与疾病的严重程度直接相关。ZIKV-NS1在脑微血管内皮细胞（BMVEC）附近的存在会影响血脑屏障，它由紧密连接（TJ）和粘附连接（AJ）组成。病毒利用不同的策略来规避这种进入大脑的障碍。本研究证明了ZMVV-NS1蛋白暴露在BMVECs中的连接完整性破坏机制。跨内皮电阻和荧光素钠迁移试验揭示了暴露于ZIKV-NS1的BMVEC在不同时间（12小时和24小时）和剂量（500 ng / mL，1000 ng / mL和1500 ng / mL）的内皮屏障破坏。ZIKV-NS1在BMVEC上的暴露导致旁观者通过分泌的ZIKV-NS1引起AJ的磷酸化和TJ的抑制。NADPH依赖的活性氧活性和氧化还原敏感的酪氨酸激酶的激活进一步增加了AJs的磷酸化。磷酸酶表达的降低导致AJ的磷酸化增加。氯化二苯撑碘化铵处理可拯救暴露于ZIKV-NS1的BMVECs中的磷酸酶和TJs表达，并抑制激酶和AJs的表达。磷酸酶表达的降低导致AJ的磷酸化增加。氯化二苯撑碘化铵处理可拯救暴露于ZIKV-NS1的BMVECs中的磷酸酶和TJs表达，并抑制激酶和AJs的表达。磷酸酶表达的降低导致AJ的磷酸化增加。氯化二苯撑碘化铵处理可拯救暴露于ZIKV-NS1的BMVECs中的磷酸酶和TJs表达，并抑制激酶和AJs的表达。