Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys
| Autor: | Mark G. Lewis, Amanda J. Martinot, Dan H. Barouch, Erica N. Borducchi, Peter J. Didier, Roderick T. Bronson, Anna K. Prohl, Onur Afacan, Deborah E. Weiss, Edward Yang, Peter Abbink, Rafael De La Barrera, Simon K. Warfield, Jonathan L. Hecht, Rebecca Peterson, Melissa Ferguson, William Rinaldi, Rafael A. Larocca |
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| Rok vydání: | 2018 |
| Předmět: |
Vasculitis
0301 basic medicine Pathology medicine.medical_specialty Apoptosis Gestational Age Viremia Neuropathology Biology Severity of Illness Index Article General Biochemistry Genetics and Molecular Biology Zika virus Necrosis 03 medical and health sciences Fetus 0302 clinical medicine Neural Stem Cells Pregnancy medicine Animals Neurons Zika Virus Infection Brain Calcinosis Zika Virus medicine.disease biology.organism_classification Macaca mulatta Magnetic Resonance Imaging 030104 developmental biology Animals Newborn Gliosis Gestation Female medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Cell. 173:1111-1122.e10 |
| ISSN: | 0092-8674 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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