Neuroanatomical abnormalities in a nonhuman primate model of congenital Zika virus infection

Danielle Beckman, Adele M.H. Seelke, Jeffrey Bennett, Paige Dougherty, Koen K.A. Van Rompay, Rebekah Keesler, Patricia A. Pesavento, Lark L.A. Coffey, John H. Morrison, Eliza Bliss-Moreau

Research output: Contribution to journalArticlepeer-review

Abstract

We evaluated neuropathological consequences of fetal ZIKV exposure in rhesus monkeys, a translatable animal model for human neural development, by carrying out quantitative neuroanatomical analyses of the nearly full-term brains of fetuses infected with ZIKV and procedure-matched controls. For each animal, a complete cerebral hemisphere was evaluated using immunohistochemical (IHC) and neuroanatomical techniques to detect virus, identify affected cell types, and evaluate gross neuroanatomical abnormalities. IHC staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the visual pathway. Regional differences tracked with the developmental timing of the brain, suggesting inflammatory processes related to viral infiltration swept through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age.

Original languageEnglish (US)
JournaleLife
Volume11
DOIs
StatePublished - Mar 9 2022
Externally publishedYes

Keywords

  • fetal
  • infectious disease
  • microbiology
  • neuroanatomy
  • neuropathology
  • neuroscience
  • rhesus macaque
  • Zika virus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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