@article{b5644a27dd774c609cdaf9f0ad7047e7,
title = "Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors",
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: Mechanisms by which Zika virus leads to microcephaly are poorly understood. Here, Li et al. demonstrate the Zika protease, required for viral replication, associates with host proteins and cleaves Septin-2, a protein required for neural cell division.",
keywords = "Zika, activated caspase, cytokinesis, microcephaly, protease, septin",
author = "Hongda Li and Laura Saucedo-Cuevas and Ling Yuan and Danica Ross and Anide Johansen and Daniel Sands and Valentina Stanley and {Guemez Gamboa}, {Alicia Dione} and Anne Gregor and Todd Evans and Shuibing Chen and Lei Tan and Henrik Molina and Nicholas Sheets and Shiryaev, {Sergey A.} and Terskikh, {Alexey V.} and Gladfelter, {Amy S.} and Sujan Shresta and Zhiheng Xu and Gleeson, {Joseph G.}",
note = "Funding Information: We thank Alex Strongin from Sanford-Burnham-Prebys Discovery Institute for the ZIKV NS2B3 clone; Guo-li Ming and Hongjun Song from University of Pennsylvania for NS2B and NS3 clones; Amy Gladfelter from UNC for Septin clones; the Rockefeller University Bio-imaging Resource Center; Kevin Cannon at The University of North Carolina at Chapel Hill; Oswald Quehenberger, Aaron Armando, and Milda Simonaitis at the UCSD Lipidomics Core; and Alysson Muotri, Alexey Terskikh, Charles Rice, Margaret MacDonald, and Edward Holmes for discussions. H.L. is supported by a Druckenmiller Fellowship from the New York Stem Cell Foundation. The work was supported by NIH grant R01 NS106387 to J.G.G., A.V.T., and S.S. J.G.G. is an Investigator with the Howard Hughes Medical Institute. The Sohn Conference Foundation and the Leona M. and Harry B. Helmsley Charitable Trust are acknowledged for mass spectrometry instrumentation. Funding Information: We thank Alex Strongin from Sanford-Burnham-Prebys Discovery Institute for the ZIKV NS2B3 clone; Guo-li Ming and Hongjun Song from University of Pennsylvania for NS2B and NS3 clones; Amy Gladfelter from UNC for Septin clones; the Rockefeller University Bio-imaging Resource Center; Kevin Cannon at The University of North Carolina at Chapel Hill; Oswald Quehenberger, Aaron Armando, and Milda Simonaitis at the UCSD Lipidomics Core; and Alysson Muotri, Alexey Terskikh, Charles Rice, Margaret MacDonald, and Edward Holmes for discussions. H.L. is supported by a Druckenmiller Fellowship from the New York Stem Cell Foundation . The work was supported by NIH grant R01 NS106387 to J.G.G., A.V.T., and S.S. J.G.G. is an Investigator with the Howard Hughes Medical Institute . The Sohn Conference Foundation and the Leona M. and Harry B. Helmsley Charitable Trust are acknowledged for mass spectrometry instrumentation. Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = mar,
day = "20",
doi = "10.1016/j.neuron.2019.01.010",
language = "English (US)",
volume = "101",
pages = "1089--1098.e4",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}
