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

Hongda Li, Laura Saucedo-Cuevas, Ling Yuan, Danica Ross, Anide Johansen, Daniel Sands, Valentina Stanley, Alicia Guemez-Gamboa, Anne Gregor, Todd Evans, Shuibing Chen, Lei Tan, Henrik Molina, Nicholas Sheets, Sergey A. Shiryaev, Alexey V. Terskikh, Amy S. Gladfelter, Sujan Shresta, Zhiheng Xu, Joseph G. Gleeson

Onderzoeksoutput: Articlepeer review

43 Citaten (Scopus)

Samenvatting

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.
Originele taal-2English
Pagina's (van-tot)1089-1098.e4
Aantal pagina's10
TijdschriftNeuron
Volume101
Nummer van het tijdschrift6
DOI's
StatusPublished - 20 mrt 2019

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