Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain

Waldorf, Kristina M. AdamsGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology (author)

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Nelson, B. R. (author)
Stencel-Baerenwald, J. E. (author)
Studholme, C. (author)
Kapur, R. P. (author)
Armistead, B. (author)
Walker, C. L. (author)
Merillat, S. (author)
Vornhagen, J. (author)
Tisoncik-Go, J. (author)
Baldessari, A. (author)
Coleman, M. (author)
Dighe, M. K. (author)
Shaw, D. W. W. (author)
Roby, J. A. (author)
Santana-Ufret, V. (author)
Boldenow, E. (author)
Li, J. W. (author)
Gao, X. H. (author)
Davis, M. A. (author)
Swanstrom, J. A. (author)
Jensen, K. (author)
Widman, D. G. (author)
Baric, R. S. (author)
Medwid, J. T. (author)
Hanley, K. A. (author)
Ogle, J. (author)
Gough, G. M. (author)
Lee, W. (author)
English, C. (author)
Durning, W. M. (author)
Thiel, J. (author)
Gatenby, C. (author)
Dewey, E. C. (author)
Fairgrieve, M. R. (author)
Hodge, R. D. (author)
Grant, R. F. (author)
Kuller, L. (author)
Dobyns, W. B. (author)
Hevner, R. F. (author)
Gale, M. (author)
Rajagopal, L. (author)
Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi (creator_code:org_t)

In:Nature Medicine: Springer Science and Business Media LLC24:3, s. 368-3741078-89561546-170X

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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