| Literature DB >> 30713029 |
Hongda Li1, Laura Saucedo-Cuevas1, Ling Yuan2, Danica Ross3, Anide Johansen1, Daniel Sands3, Valentina Stanley3, Alicia Guemez-Gamboa1, Anne Gregor1, Todd Evans4, Shuibing Chen4, Lei Tan4, Henrik Molina5, Nicholas Sheets6, Sergey A Shiryaev7, Alexey V Terskikh7, Amy S Gladfelter8, Sujan Shresta6, Zhiheng Xu2, Joseph G Gleeson9.
Abstract
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.Entities:
Keywords: Zika; activated caspase; cytokinesis; microcephaly; protease; septin
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Year: 2019 PMID： 30713029 PMCID： PMC6690588 DOI： 10.1016/j.neuron.2019.01.010
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173