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 language | English (US) |
|---|---|
| Article number | 263 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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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 journal › Article
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TY - JOUR
T1 - Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology
AU - Hirsch, Alec
AU - Roberts, Victoria
AU - Grigsby, Peta
AU - Haese, Nicole
AU - Schabel, Matthias
AU - Wang, Xiaojie
AU - Lo, Jamie
AU - Liu, Zheng
AU - Kroenke, Christopher (Chris)
AU - Smith, Jessica L.
AU - Kelleher, Meredith
AU - Broeckel, Rebecca
AU - Kreklywich, Craig N.
AU - Parkins, Christopher J.
AU - Denton, Michael
AU - Smith, Patricia
AU - De Filippis, Victor
AU - Messer, William
AU - Nelson, Jay
AU - Hennebold, Jon
AU - Grafe, Marjorie
AU - Colgin, Lois
AU - Lewis, Anne
AU - Ducore, Rebecca
AU - Swanson, Tonya
AU - Legasse, Alfred W.
AU - Axthelm, Michael
AU - MacAllister, Rhonda
AU - Moses, Ashlee
AU - Morgan, Terry
AU - Frias, Antonio
AU - Streblow, Daniel
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041397899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041397899&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-02499-9
DO - 10.1038/s41467-017-02499-9
M3 - Article
C2 - 29343712
AN - SCOPUS:85041397899
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 263
ER -