Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease
Authors: Lark L Coffey
Jodie Usachenko
Wilhelm von Morgenland
Anil Singapuri
John H Morrison
Robert Orr
Kenneth Jackson
Victoria A Heng
Pietro Presicce
Eliza Bliss-Moreau
Anne M Gibbons
Tracy MacGill
Sallie Permar
Patricia A Pesavento
Koen K A Van Rompay
Suhas G Kallapur
Christina Cruzen
Amir Ardeshir
J Rachel Reader
Rebekah I Keesler
Jennifer Watanabe
JoAnn Yee
Holly Heimsath
Kari L Christe
Richard McFarland
Kui Gao
Michelle McClure
Kevin Woolard
Paranthaman Senthamaraikannan
Jeffrey M Linnen
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: Zika virus; fetal microcephaly; neurologic defects; non-human primate model; fetal pathogenesis
Affiliations: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. ., California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA., Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA, 95616, USA., Donders Institute, Radboud University, Montessorilaan 3, 6525 HR, Nijmegen, The Netherlands., Department of Psychology, University of California, 1 Shields Avenue, Davis, CA, 95616, USA., Duke Human Vaccine Institute, Duke University Medical Center, 103020, 2 Genome Court MSRBII, Durham, NC, 27710, USA., Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA., 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., Grifols Diagnostic Solutions, Inc., 10808 Willow Court, San Diego, CA, 92127, USA., Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Food and Drug Administration, 25 New Hampshire Avenue, Silver Spring, MD, 20903, USA., 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., The Advanced Regenerative Manufacturing Institute, 400 Commercial Street, Manchester, NH, 03101, USA., California National Primate Research Center, University of California, 1 Shields Avenue, Davis, CA, 95616, USA. .

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. 

Retracted: No

PubPeer comments:
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