Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

TitleFetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.
Publication TypeJournal Article
Year of Publication2018
AuthorsMartinot AJ, Abbink P, Afacan O, Prohl AK, Bronson R, Hecht JL, Borducchi EN, Larocca RA, Peterson RL, Rinaldi W, Ferguson M, Didier PJ, Weiss D, Lewis MG, De La Barrera RA, Yang E, Warfield SK, Barouch DH
JournalCell
Volume173
Issue5
Pagination1111-1122.e10
Date Published05/17/2018
ISSN1097-4172
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.

DOI10.1016/j.cell.2018.03.019
Alternate JournalCell
PubMed ID29606355
PubMed Central IDPMC5959775
Grant ListU19 AI096040 / AI / NIAID NIH HHS / United States
U19 AI128751 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
UM1 AI124377 / AI / NIAID NIH HHS / United States
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