Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys

Amanda J. Martinot, Peter Abbink, Onur Afacan, Anna K. Prohl, Roderick Bronson, Jonathan L. Hecht, Erica N. Borducchi, Rafael A. Larocca, Rebecca L. Peterson, William Rinaldi, Melissa Ferguson, Peter J. Didier, Deborah Weiss, Mark G. Lewis, Rafael A. De La Barrera, Edward Yang, Simon K. Warfield, Dan H. Barouch

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

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. ZIKV infection in early pregnant female rhesus monkeys resulted in fetal neuropathology with vascular compromise and neuroprogenitor cell dysfunction, similar to congenital ZIKV syndrome in human infants.

Original languageEnglish
Pages (from-to)1111-1122.e10
JournalCell
Volume173
Issue number5
DOIs
StatePublished - 17 May 2018
Externally publishedYes

Keywords

  • Zikavirus
  • neonate
  • neuropathology
  • non-human primate
  • placenta
  • pregnancy

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