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

Lark L. Coffey (), Rebekah I. Keesler, Patricia A. Pesavento, Kevin Woolard, Anil Singapuri, Jennifer Watanabe, Christina Cruzen, Kari L. Christe, Jodie Usachenko, JoAnn Yee, Victoria A. Heng, Eliza Bliss-Moreau, J. Rachel Reader, Wilhelm Morgenland, Anne M. Gibbons, Kenneth Jackson, Amir Ardeshir, Holly Heimsath, Sallie Permar, Paranthaman Senthamaraikannan, Pietro Presicce, Suhas G. Kallapur, Jeffrey M. Linnen, Kui Gao, Robert Orr, Tracy MacGill, Michelle McClure, Richard McFarland, John H. Morrison and Koen K. A. Rompay ()
Additional contact information
Lark L. Coffey: University of California
Rebekah I. Keesler: University of California
Patricia A. Pesavento: University of California
Kevin Woolard: University of California
Anil Singapuri: University of California
Jennifer Watanabe: University of California
Christina Cruzen: University of California
Kari L. Christe: University of California
Jodie Usachenko: University of California
JoAnn Yee: University of California
Victoria A. Heng: University of California
Eliza Bliss-Moreau: University of California
J. Rachel Reader: University of California
Wilhelm Morgenland: University of California
Anne M. Gibbons: University of California
Kenneth Jackson: University of California
Amir Ardeshir: University of California
Holly Heimsath: Duke University Medical Center
Sallie Permar: Duke University Medical Center
Paranthaman Senthamaraikannan: Cincinnati Children’s Hospital Research Foundation
Pietro Presicce: David Geffen School of Medicine at the University of California
Suhas G. Kallapur: David Geffen School of Medicine at the University of California
Jeffrey M. Linnen: Grifols Diagnostic Solutions, Inc.
Kui Gao: Grifols Diagnostic Solutions, Inc.
Robert Orr: Food and Drug Administration
Tracy MacGill: Food and Drug Administration
Michelle McClure: Food and Drug Administration
Richard McFarland: The Advanced Regenerative Manufacturing Institute
John H. Morrison: University of California
Koen K. A. Rompay: University of California

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04777-6

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