{
  "abstract": "Zika virus (ZIKV) infection during early development is associated with severe neurodevelopmental impairment, including congenital microcephaly, yet the molecular mechanisms linking viral exposure to neuronal dysfunction remain incompletely understood. Ndel1 (nudE neurodevelopment protein 1 like 1) is an oligopeptidase critically involved in neuronal migration, neurite outgrowth, and cytoskeletal dynamics, processes essential for proper brain development. Building on previous observations that Ndel1 enzymatic activity is reduced in ZIKV-infected embryonic and neonatal brains, we investigated whether this modulation represents a conserved host response or a strain-specific molecular effect. Using a neonatal intracerebroventricular infection model in Swiss mice at postnatal day 0, we compared the effects of a Brazilian ZIKV strain (ZIKVBR), an African lineage strain (ZIKVAF), and dengue virus (DENV) on Ndel1 regulation in the brain. We found that Ndel1 enzymatic activity was significantly reduced at early post-infection time points (P3 and P7) exclusively in ZIKVBR-infected animals, whereas ZIKVAF and DENV did not alter enzyme activity relative to controls. Notably, at the earliest timepoint (P3), this reduction occurred in the absence of changes in Ndel1 mRNA expression, indicating an initial post-transcriptional or functional mechanism of regulation, although Ndel1 mRNA expression was also significantly reduced by P7. Although both ZIKV strains induced robust inflammatory gene expression, only ZIKVBR infection resulted in decreased Ndel1 activity, dissociating neuroinflammatory signaling from enzymatic modulation. Importantly, this strain-specific reduction parallels the unique capacity of ZIKVBR to induce microcephaly and supports Ndel1 dysfunction as an early molecular event associated with neurodevelopmental impairment. Together, these findings identify a virus- and strain-specific regulation of a key neuronal enzyme and provide mechanistic insight into the molecular basis of ZIKVBR-associated neurodevelopmental outcomes.\n\nGraphical Abstract:",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), R. Três de Maio, 100-Vila Clementino, São Paulo, SP 04044-020 Brazil",
    "Instituto de Ciências Biomédicas, Universidade Federal Do Rio de Janeiro (UFRJ), R. Manoel Frota Moreira, 1 andar—Cidade Universitária, Rio de Janeiro, RJ 21941-902 Brazil",
    "Instituto de Biologia - Laboratório de Virologia Molecular, Departamento de Genética, Universidade Federal Do Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, 373-Sala A1-050-Cidade Universitária, Rio de Janeiro, RJ 21941-902 Brazil",
    "Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, 16 De Crespigny Park-Denmark Hill, London, SE5 8AF UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ingrid S. de Farias",
      "orcid": "0000-0002-0443-3669"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana P. Ximenes",
      "orcid": "0009-0008-0472-8556"
    },
    {
      "affs": [
        0
      ],
      "name": "William Y. Oyadomari",
      "orcid": "0009-0003-2654-417X"
    },
    {
      "affs": [
        1
      ],
      "name": "Raissa Rilo Christoff",
      "orcid": "0000-0002-7052-2643"
    },
    {
      "affs": [
        0
      ],
      "name": "João V. S. Nani",
      "orcid": "0000-0002-4336-1709"
    },
    {
      "affs": [
        2
      ],
      "name": "Tailene Rabello",
      "orcid": "0000-0002-6720-1013"
    },
    {
      "affs": [
        2
      ],
      "name": "Luiza M. Higa",
      "orcid": "0000-0003-2622-534X"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Patrícia P. Garcez",
      "orcid": "0000-0002-9107-1335"
    },
    {
      "affs": [
        0
      ],
      "name": "Mirian A. F. Hayashi",
      "orcid": "0000-0001-6437-4923"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgx5jyrjhqa5f.bib",
  "cited_by": 0,
  "doi": "10.1007/s10571-026-01798-4",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13755227/",
  "id": "fgx5jyrjhqa5f",
  "issns": [
    "0272-4340",
    "1573-6830"
  ],
  "landing_url": "https://doi.org/10.1007/s10571-026-01798-4",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2739|Mosquito-borne diseases and control"
    ]
  ],
  "openalex": "W7203603262",
  "pdf_url": null,
  "pmcid": "PMC13755227",
  "pmid": "43015419",
  "published": "2026-08-17",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/fgx5jyrjhqa5f.ris",
  "sources": [
    {
      "first_seen": "2026-11-15T12:24:05Z",
      "native_id": "PMC13755227",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10571-026-01798-4"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Mosquito-borne diseases and control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Strain-Specific Reduction of Ndel1 Enzymatic Activity During Early Zika Virus Infection in the Neonatal Brain",
  "title_text": "Strain-Specific Reduction of Ndel1 Enzymatic Activity During Early Zika Virus Infection in the Neonatal Brain",
  "type": "peer-reviewed",
  "updated_at": "2026-11-15T12:24:05Z",
  "url": "https://research.draconitic.com/paper/fgx5jyrjhqa5f",
  "venue": "Cellular and Molecular Neurobiology",
  "versions": []
}