ArticleNeuron2019
Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- The Flavivirus NS3 Protein: Its Multifaceted Roles and Therapeutic Potential.Journal of medical virology · 2026Review
- Coiled-coil homo-oligomerization and disaggregase Hsp104 act in parallel to stabilize orphan septins.bioRxiv : the preprint server for biology · 2026Article
- ZIKV envelope protein is a strong blocker of early directional differentiation in the neural lineage.Communications biology · 2026Article
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- Host protein cleavage by Dengue and Zika virus NS3 proteases: from substrate identification to potential biological consequences.Frontiers in cellular and infection microbiology · 2026Review
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Emerging Arthropod-Borne Viruses Hijack the Host Cell Cytoskeleton During Neuroinvasion.Viruses · 2025Review
- Turnip mosaic virus infection cleaves MEDIATOR SUBUNIT16 in plants increasing plant susceptibility to the virus and its aphid vector Myzus persicae.BMC plant biology · 2025Article
- Towards a Universal Translator: Decoding the PTMs That Regulate Orthoflavivirus Infection.Viruses · 2025Review
- Cleavage of SQSTM1/p62 by the Zika virus protease NS2B3 prevents autophagic degradation of viral NS3 and NS5 proteins.Autophagy · 2024Article
- Erp57 facilitates ZIKV-induced DNA damage via NS2B/NS3 complex formation.Emerging microbes & infections · 2024Article
- Orthoflaviviral Inhibitors in Clinical Trials, Preclinical In Vivo Efficacy Targeting NS2B-NS3 and Cellular Antiviral Activity via Competitive Protease Inhibition.Molecules (Basel, Switzerland) · 2024Review
- Review
- The Inhibition of NS2B/NS3 Protease: A New Therapeutic Opportunity to Treat Dengue and Zika Virus Infection.International journal of molecular sciences · 2024Review
- Unearthing the role of septins in viral infections.Bioscience reports · 2024Review
- The "microcephalic hydrocephalus" paradox as a paradigm of altered neural stem cell biology.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Proteomics and Metabolomics in Congenital Zika Syndrome: A Review of Molecular Insights and Biomarker Discovery.Advances in experimental medicine and biology · 2024Review
- SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway.Nature communications · 2023Article
- Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly.Nature communications · 2023Article
- Bioinformatics Analysis and Experimental Verification of Exercise for Aging Mice in Different Brain Regions Based on Transcriptome Sequencing.Life (Basel, Switzerland) · 2023Article
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Authors and funding
20 authors at 11 institutions in 2 countries.
Hongda LiLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Laura Saucedo-CuevasLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Ling YuanInstitute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Danica RossHoward Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Anide JohansenLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Daniel SandsHoward Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Valentina StanleyHoward Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Alicia Guemez-GamboaLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Anne GregorLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.
Todd EvansDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Shuibing ChenDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Lei TanDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Henrik MolinaProteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.
Nicholas SheetsLa Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Sergey A ShiryaevSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Alexey V TerskikhSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Amy S GladfelterDepartment of Biology, Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sujan ShrestaLa Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Zhiheng XuInstitute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Joseph G GleesonLaboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA. Electronic address: jogleeson@ucsd.edu.
Children’s Institute · USHoward Hughes Medical Institute · USRockefeller University · USCornell University · USInstitute of Genetics and Developmental Biology · CNLa Jolla Institute for Immunology · USDiscovery Institute · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of California, San Diego · USUniversity of North Carolina at Chapel Hill · USWeill Cornell Medicine · US
Funding
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0MMolecular basis of Zika-induced microcephalyR01NS106387 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2018 to 2021
$2.2MNINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS106387
Abstract
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.
Indexed as
ApoptosisCytokinesisMitosisCytoskeletonDEAD-box RNA HelicasesHEK293 CellsHeLa CellsHumansNeural Stem CellsNeurogenesisNucleoside-TriphosphataseRNA HelicasesSeptinsSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesDEAD-box RNA HelicasesNS2B protein, flavivirusNS3 protein, flavivirusNucleoside-TriphosphataseRNA HelicasesSEPTIN2 protein, humanSeptinsSerine EndopeptidasesViral Nonstructural ProteinsViral Proteasesactivated caspasecytokinesismicrocephalyproteaseseptinZika
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