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

被引:9
作者
Beckman, Danielle [1 ]
Seelke, Adele M. H. [1 ,2 ]
Bennett, Jeffrey [1 ,2 ]
Dougherty, Paige [1 ,2 ]
Van Rompay, Koen K. A. [1 ,3 ]
Keesler, Rebekah [1 ]
Pesavento, Patricia A. [3 ]
Coffey, Lark L. A. [3 ]
Morrison, John H. [1 ,4 ]
Bliss-Moreau, Eliza [1 ,2 ]
机构
[1] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA
[3] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA USA
[4] Univ Calif Davis, Dept Neurol, Sch Med, Davis, CA USA
关键词
Zika virus; fetal; neuroanatomy; neuropathology; Rhesus macaque; NEONATAL AMYGDALA; RETINAL LESIONS; VISUAL-SYSTEM; INFANTS; CHILDREN; GRADIENTS; CORTEX; CELLS; MICE; GLIA;
D O I
10.7554/eLife.64734
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:26
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