Hartman Institute for Therapeutic Organ Regeneration

Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors.

TitleZika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors.
Publication TypeJournal Article
Year of Publication2019
AuthorsLi 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
JournalNeuron
Volume101
Issue6
Pagination1089-1098.e4
Date Published2019 Mar 20
ISSN1097-4199
KeywordsApoptosis, 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>

DOI10.1016/j.neuron.2019.01.010
Alternate JournalNeuron
PubMed ID30713029
PubMed Central IDPMC6690588
Grant ListP30 NS047101 / NS / NINDS NIH HHS / United States
R01 NS106387 / NS / NINDS NIH HHS / United States

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