Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys

Cell. 2018 May 17;173(5):1111-1122.e10. doi: 10.1016/j.cell.2018.03.019. Epub 2018 Mar 29.


The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

Keywords: Zikavirus; neonate; neuropathology; non-human primate; placenta; pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain / diagnostic imaging
  • Brain / pathology
  • Calcinosis / pathology
  • Calcinosis / veterinary
  • Female
  • Fetus / virology*
  • Gestational Age
  • Macaca mulatta
  • Magnetic Resonance Imaging
  • Necrosis
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / virology
  • Neurons / pathology*
  • Neurons / virology
  • Pregnancy
  • Severity of Illness Index
  • Vasculitis / pathology
  • Vasculitis / veterinary
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / pathology*
  • Zika Virus Infection / veterinary
  • Zika Virus Infection / virology