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Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors
- Li, Hongda;
- Saucedo-Cuevas, Laura;
- Yuan, Ling;
- Ross, Danica;
- Johansen, Anide;
- Sands, Daniel;
- Stanley, Valentina;
- Guemez-Gamboa, Alicia;
- Gregor, Anne;
- Evans, Todd;
- Chen, Shuibing;
- Tan, Lei;
- Molina, Henrik;
- Sheets, Nicholas;
- Shiryaev, Sergey A;
- Terskikh, Alexey V;
- Gladfelter, Amy S;
- Shresta, Sujan;
- Xu, Zhiheng;
- Gleeson, Joseph G
Published Web Location
https://doi.org/10.1016/j.neuron.2019.01.010Abstract
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.
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