Title | Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Li H, Saucedo-Cuevas L, Yuan L, Ross D, Johansen A, Sands D, Stanley V, Guemez-Gamboa A, Gregor A, Evans T, Chen S, Tan L, Molina H, Sheets N, Shiryaev SA, Terskikh AV, Gladfelter AS, Shresta S, Xu Z, Gleeson JG |
Journal | Neuron |
Volume | 101 |
Issue | 6 |
Pagination | 1089-1098.e4 |
Date Published | 2019 Mar 20 |
ISSN | 1097-4199 |
Keywords | Apoptosis, Cytokinesis, Cytoskeleton, HEK293 Cells, HeLa Cells, Humans, Mitosis, Neural Stem Cells, Neurogenesis, RNA Helicases, Septins, Serine Endopeptidases, Viral Nonstructural Proteins, Zika Virus |
Abstract | <p>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.</p> |
DOI | 10.1016/j.neuron.2019.01.010 |
Alternate Journal | Neuron |
PubMed ID | 30713029 |
PubMed Central ID | PMC6690588 |
Grant List | P30 NS047101 / NS / NINDS NIH HHS / United States R01 NS106387 / NS / NINDS NIH HHS / United States |