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

Author

Listed:
  • 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
    Radboud University)

  • Eliza Bliss-Moreau

    (University of California
    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)

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.

Suggested Citation

  • 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 &, 2018. "Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04777-6
    DOI: 10.1038/s41467-018-04777-6
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    Cited by:

    1. Jennifer Tisoncik-Go & Caleb Stokes & Leanne S. Whitmore & Daniel J. Newhouse & Kathleen Voss & Andrew Gustin & Cheng-Jung Sung & Elise Smith & Jennifer Stencel-Baerenwald & Edward Parker & Jessica M., 2024. "Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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