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

Alec Hirsch, Victoria Roberts, Peta Grigsby, Nicole Haese, Matthias Schabel, Xiaojie Wang, Jamie Lo, Zheng Liu, Christopher (Chris) Kroenke, Jessica L. Smith, Meredith Kelleher, Rebecca Broeckel, Craig N. Kreklywich, Christopher J. Parkins, Michael Denton, Patricia Smith, Victor De Filippis, William Messer, Jay Nelson, Jon HenneboldMarjorie Grafe, Lois Colgin, Anne Lewis, Rebecca Ducore, Tonya Swanson, Alfred W. Legasse, Michael Axthelm, Rhonda MacAllister, Ashlee Moses, Terry Morgan, Antonio Frias, Daniel Streblow

Research output: Contribution to journalArticle

35 Citations (Scopus)

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

Fingerprint

viruses
infectious diseases
Fetal Development
Macaca mulatta
Viruses
Oxygen
causes
Placenta
pathology
Pathology
oxygen
Mothers
Nervous System Malformations
Chorionic Villi
Vasculitis
Growth and Development
central nervous system
animal models
pregnancy
fetuses

ASJC Scopus subject areas

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

Cite this

Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. / Hirsch, Alec; Roberts, Victoria; Grigsby, Peta; Haese, Nicole; Schabel, Matthias; Wang, Xiaojie; Lo, Jamie; Liu, Zheng; Kroenke, Christopher (Chris); Smith, Jessica L.; Kelleher, Meredith; Broeckel, Rebecca; Kreklywich, Craig N.; Parkins, Christopher J.; Denton, Michael; Smith, Patricia; De Filippis, Victor; Messer, William; Nelson, Jay; Hennebold, Jon; Grafe, Marjorie; Colgin, Lois; Lewis, Anne; Ducore, Rebecca; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael; MacAllister, Rhonda; Moses, Ashlee; Morgan, Terry; Frias, Antonio; Streblow, Daniel.

In: Nature Communications, Vol. 9, No. 1, 263, 01.12.2018.

Research output: Contribution to journalArticle

Hirsch, Alec ; Roberts, Victoria ; Grigsby, Peta ; Haese, Nicole ; Schabel, Matthias ; Wang, Xiaojie ; Lo, Jamie ; Liu, Zheng ; Kroenke, Christopher (Chris) ; Smith, Jessica L. ; Kelleher, Meredith ; Broeckel, Rebecca ; Kreklywich, Craig N. ; Parkins, Christopher J. ; Denton, Michael ; Smith, Patricia ; De Filippis, Victor ; Messer, William ; Nelson, Jay ; Hennebold, Jon ; Grafe, Marjorie ; Colgin, Lois ; Lewis, Anne ; Ducore, Rebecca ; Swanson, Tonya ; Legasse, Alfred W. ; Axthelm, Michael ; MacAllister, Rhonda ; Moses, Ashlee ; Morgan, Terry ; Frias, Antonio ; Streblow, Daniel. / Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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