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 Dione 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1089-1098.e4
Issue number6
StatePublished - Mar 20 2019


  • Zika
  • activated caspase
  • cytokinesis
  • microcephaly
  • protease
  • septin

ASJC Scopus subject areas

  • Neuroscience(all)


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