[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Cell. 2018 Mar 28. pii: S0092-8674(18)30299-X. doi: 10.1016/j.cell.2018.03.019. [Epub ahead of print]
Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.
Martinot AJ1, Abbink P1, Afacan O2, Prohl AK2, Bronson R3, Hecht JL4, Borducchi EN1, Larocca RA1, Peterson RL1, Rinaldi W5, Ferguson M5, Didier PJ6, Weiss D7, Lewis MG7, De La Barrera RA8, Yang E2, Warfield SK2, Barouch DH9.
Author information: 1 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. 2 Computational Radiology Laboratory, Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 3 Harvard Medical School, Boston, MA 02115, USA. 4 Division of Anatomic Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. 5 Alphagenesis, Yemassee, SC 29945, USA. 6 Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA. 7 Bioqual, Rockville, MD 20852, USA. 8 Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. 9 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: email@example.com.
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
PMID: 29606355 DOI: 10.1016/j.cell.2018.03.019
Keywords: Zika Virus; Pregnancy; Zika Congenital Infection; Animal Models.