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Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys

2018; Cell Press; Volume: 173; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2018.03.019

1097-4172

Amanda J. Martinot, Peter Abbink, Onur Afacan, Anna K. Prohl, Roderick T. Bronson, Jonathan L. Hecht, Erica N. Borducchi, Rafael A. Larocca, Rebecca 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,

Virology and Viral Diseases

Highlights•ZIKV infection in early pregnancy leads to fetal neuropathology in rhesus monkeys•Placental pathology in ZIKV-infected dams is associated with severe fetal pathology•Key features include vascular compromise and neuroprogenitor cell proliferationSummaryThe 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.Graphical abstract