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Nat Commun. 2018 Jun 20;9(1):2414. doi: 10.1038/s41467-018-04777-6.

Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease.

Author information

1
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. lcoffey@ucdavis.edu.
2
California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA.
3
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA.
4
Donders Institute, Radboud University, Montessorilaan 3, 6525 HR, Nijmegen, The Netherlands.
5
Department of Psychology, University of California, 1 Shields Avenue, Davis, CA, 95616, USA.
6
Duke Human Vaccine Institute, Duke University Medical Center, 103020, 2 Genome Court MSRBII, Durham, NC, 27710, USA.
7
Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
8
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
9
Grifols Diagnostic Solutions, Inc., 10808 Willow Court, San Diego, CA, 92127, USA.
10
Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Food and Drug Administration, 25 New Hampshire Avenue, Silver Spring, MD, 20903, USA.
11
Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20903, USA.
12
The Advanced Regenerative Manufacturing Institute, 400 Commercial Street, Manchester, NH, 03101, USA.
13
California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. kkvanrompay@ucdavis.edu.

Abstract

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.

PMID:
29925843
PMCID:
PMC6010452
DOI:
10.1038/s41467-018-04777-6
[Indexed for MEDLINE]
Free PMC Article

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