Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors.
Zika
activated caspase
cytokinesis
microcephaly
protease
septin
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
20 03 2019
20 03 2019
Historique:
received:
09
05
2018
revised:
17
10
2018
accepted:
31
12
2018
pubmed:
5
2
2019
medline:
5
11
2019
entrez:
5
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30713029
pii: S0896-6273(19)30011-X
doi: 10.1016/j.neuron.2019.01.010
pmc: PMC6690588
mid: NIHMS1040697
pii:
doi:
Substances chimiques
NS2B protein, flavivirus
0
NS3 protein, flavivirus
0
Viral Nonstructural Proteins
0
Serine Endopeptidases
EC 3.4.21.-
SEPTIN2 protein, human
EC 3.6.1.-
Septins
EC 3.6.1.-
RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
1089-1098.e4Subventions
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106387
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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