Sex- and age-specific development of ssRNA virus receptor expression in the human brain
- 1McMaster Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.
- 2Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario, Canada.
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.
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BibTeX
@article{monteiro2026agespecific,
title = {{Sex- and age-specific development of ssRNA virus receptor expression in the human brain}},
author = {Leanne Monteiro and Negeen Halabian and Jiawei Li and Maheshwar Panday and Nadine Barone and Peiyi Wang and Kathryn M Murphy},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360526},
url = {https://doi.org/10.1371/journal.pone.0360526},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sex- and age-specific development of ssRNA virus receptor expression in the human brain
AU - Leanne Monteiro
AU - Negeen Halabian
AU - Jiawei Li
AU - Maheshwar Panday
AU - Nadine Barone
AU - Peiyi Wang
AU - Kathryn M Murphy
PY - 2026
DA - 2026/10/29
JO - PLOS One
DO - 10.1371/journal.pone.0360526
UR - https://doi.org/10.1371/journal.pone.0360526
AB - 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.
SN - 1932-6203
ER -