Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Neuron. 2019 Mar 20;101(6):1089-1098.e4. doi: 10.1016/j.neuron.2019.01.010. Epub 2019 Jan 31.
Zika virus (ZIKV) targets neural progenitor cells in the brain, attenuates cell proliferation, and leads to cell death. Here, we describe a role for the ZIKV protease NS2B-NS3 heterodimer in mediating neurotoxicity through cleavage of a host protein required for neurogenesis. Similar to ZIKV infection, NS2B-NS3 expression led to cytokinesis defects and cell death in a protease activity-dependent fashion. Among binding partners, NS2B-NS3 cleaved Septin-2, a cytoskeletal factor involved in cytokinesis. Cleavage of Septin-2 occurred at residue 306 and forced expression of a non-cleavable Septin-2 restored cytokinesis, suggesting a direct mechanism of ZIKV-induced neural toxicity. VIDEO ABSTRACT.
寨卡病毒（ZIKV）靶向大脑中的神经祖细胞，减弱细胞增殖，并导致细胞死亡。在这里，我们描述了 ZIKV 蛋白酶 NS2B-NS3 异二聚体通过切割神经发生所需的宿主蛋白在介导神经毒性中的作用。与 ZIKV 感染相似，NS2B-NS3 的表达导致有丝分裂缺陷和细胞死亡，这是一种依赖蛋白酶活性的方式。在结合伴侣中，NS2B-NS3 切割了参与有丝分裂的细胞骨架因子 Septin-2。Septin-2 的切割发生在残基 306 处，强制表达不可切割的 Septin-2 恢复了有丝分裂，这表明 ZIKV 诱导的神经毒性的直接机制。视频摘要。
