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

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, Rebecca Broeckel, Craig N. Kreklywich, Christopher J. Parkins, Michael Denton, Patricia Smith, Victor Defilippis, William Messer, Jay A. Nelson, Jon D. HenneboldMarjorie Grafe, Lois Colgin, Anne Lewis, Rebecca Ducore, Tonya Swanson, Alfred W. Legasse, Michael K. Axthelm, Rhonda MacAllister, Ashlee V. Moses, Terry K. Morgan, Antonio E. Frias, Daniel N. Streblow

Research output: Contribution to journalArticle

56 Scopus citations

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.

Original languageEnglish (US)
Article number263
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Hirsch, A. J., Roberts, V. H. J., Grigsby, P. L., Haese, N., Schabel, M. C., Wang, X., Lo, J. O., Liu, Z., Kroenke, C. D., Smith, J. L., Kelleher, M., Broeckel, R., Kreklywich, C. N., Parkins, C. J., Denton, M., Smith, P., Defilippis, V., Messer, W., Nelson, J. A., ... Streblow, D. N. (2018). Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nature Communications, 9(1), [263]. https://doi.org/10.1038/s41467-017-02499-9