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Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology

Author

Listed:
  • Alec J. Hirsch

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Victoria H. J. Roberts

    (ONPRC)

  • Peta L. Grigsby

    (ONPRC
    OHSU)

  • Nicole Haese

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Matthias C. Schabel

    (OHSU
    University of Utah)

  • Xiaojie Wang

    (OHSU)

  • Jamie O. Lo

    (OHSU)

  • Zheng Liu

    (OHSU)

  • Christopher D. Kroenke

    (OHSU)

  • Jessica L. Smith

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Meredith Kelleher

    (ONPRC)

  • Rebecca Broeckel

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Craig N. Kreklywich

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Christopher J. Parkins

    (Oregon Health and Science University (OHSU))

  • Michael Denton

    (Oregon Health and Science University (OHSU))

  • Patricia Smith

    (Oregon Health and Science University (OHSU))

  • Victor DeFilippis

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • William Messer

    (OHSU
    OHSU)

  • Jay A. Nelson

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Jon D. Hennebold

    (ONPRC
    OHSU)

  • Marjorie Grafe

    (OHSU)

  • Lois Colgin

    (ONPRC)

  • Anne Lewis

    (ONPRC)

  • Rebecca Ducore

    (ONPRC)

  • Tonya Swanson

    (Oregon National Primate Research Center (ONPRC))

  • Alfred W. Legasse

    (Oregon National Primate Research Center (ONPRC))

  • Michael K. Axthelm

    (Oregon National Primate Research Center (ONPRC))

  • Rhonda MacAllister

    (ONPRC)

  • Ashlee V. Moses

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

  • Terry K. Morgan

    (OHSU
    OHSU)

  • Antonio E. Frias

    (ONPRC
    OHSU)

  • Daniel N. Streblow

    (Oregon Health and Science University (OHSU)
    Oregon National Primate Research Center (ONPRC))

Abstract

Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development.

Suggested Citation

  • Alec J. Hirsch & Victoria H. J. Roberts & Peta L. Grigsby & Nicole Haese & Matthias C. Schabel & Xiaojie Wang & Jamie O. Lo & Zheng Liu & Christopher D. Kroenke & Jessica L. Smith & Meredith Kelleher , 2018. "Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02499-9
    DOI: 10.1038/s41467-017-02499-9
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