{
  "abstract": "Neurotropic single-stranded RNA (ssRNA) viruses can disrupt brain function, yet little is known about how host virus receptor expression develops across the human lifespan or whether these trajectories differ between females and males. We focused on postnatal development using postmortem transcriptomic data from 33 human donors (4 months–82 years; both sexes), comprising 52 cerebral hemispheres and 15 brain areas, to characterize developmental patterns of 67 host receptor genes that mediate entry of major ssRNA viral families. Using sex-specific LOESS trajectory modelling, hierarchical clustering, and sliding-window differential expression analyses, we identified multiple non-linear developmental programs governing virus receptor expression. About half of female–male gene–area trajectory pairs exhibited divergent developmental patterns. Sex differences were most pronounced in the cortex, where high-dimensional receptor expression profiles were sufficient to predict the sex of individual cases. Sex differential expression was most frequent during early childhood, coinciding with sensitive periods of cortical circuit refinement. A targeted prenatal analysis revealed that virus receptor expression was predominantly male-biased before birth, contrasting with the predominantly female-biased expression observed during the early postnatal period. Although receptors from most viral families were broadly distributed across developmental programs, a subset of sex-by-age expression clusters showed some enrichment for specific viral lineages and glial-associated cell-type signatures. Together, these findings reveal that virus receptor expression in the human brain is organized into structured, sex-biased trajectories that dynamically reorganize over development, providing the first developmental atlas of viral entry receptors in the human brain.",
  "abstract_shown": true,
  "affiliations": [
    "McMaster Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.",
    "Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario, Canada."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
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        0
      ],
      "name": "Leanne Monteiro"
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    {
      "affs": [
        0
      ],
      "name": "Negeen Halabian"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiawei Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Maheshwar Panday"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadine Barone",
      "orcid": "0009-0004-3651-7148"
    },
    {
      "affs": [
        1
      ],
      "name": "Peiyi Wang",
      "orcid": "0009-0004-0197-2984"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kathryn M Murphy",
      "orcid": "0000-0002-1296-0688"
    }
  ],
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  "doi": "10.1371/journal.pone.0360526",
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  "language": "eng",
  "licence": "CC-BY",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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  "native_subjects": [
    [
      "heading",
      "Animal Cells"
    ],
    [
      "heading",
      "Astrocytes"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Biology and life sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Cellular Neuroscience"
    ],
    [
      "heading",
      "Cellular Types"
    ],
    [
      "heading",
      "Cluster Analysis"
    ],
    [
      "heading",
      "Computational Biology"
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    [
      "heading",
      "Flaviviruses"
    ],
    [
      "heading",
      "Gene Expression"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Genome Analysis"
    ],
    [
      "heading",
      "Genomics"
    ],
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      "heading",
      "Glial Cells"
    ],
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      "heading",
      "Hierarchical Clustering"
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      "heading",
      "Mathematical and Statistical Techniques"
    ],
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      "heading",
      "Mathematics"
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    [
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      "Medical Microbiology"
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      "heading",
      "Medicine and Health Sciences"
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      "Microbial Genetics"
    ],
    [
      "heading",
      "Microbial Pathogens"
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      "Microglial Cells"
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    [
      "heading",
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    [
      "heading",
      "Viruses"
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      "Zika Virus"
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    [
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      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Glial cells/Macroglial cells/Astrocytes"
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      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Glial cells/Microglial cells"
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      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Flaviviruses/Zika virus"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral genetics/Viral gene expression"
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    [
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      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/RNA viruses/Flaviviruses/Zika virus"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Flaviviruses/Zika virus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Flaviviruses/Zika virus"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Statistics/Statistical methods/Regression analysis"
    ],
    [
      "plos",
      "/Research and analysis methods/Mathematical and statistical techniques/Cluster analysis/Hierarchical clustering"
    ],
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      "/Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Regression analysis"
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  "pdf_url": "https://europepmc.org/articles/PMC13718946?pdf=render",
  "pmcid": "PMC13718946",
  "pmid": "42956020",
  "published": "2026-10-29",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/ct8m7h8b80kdf.ris",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Gene Expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Computational Biology",
      "subfield": "bioinformatics"
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    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "biology",
      "origin": "plos:genomics",
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    {
      "field": "biology",
      "origin": "plos:microbiology",
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  "title": "Sex- and age-specific development of ssRNA virus receptor expression in the human brain",
  "title_text": "Sex- and age-specific development of ssRNA virus receptor expression in the human brain",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:52Z",
  "url": "https://research.draconitic.com/paper/ct8m7h8b80kdf",
  "venue": "PLOS One",
  "versions": []
}