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


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.

SUBMITTER: Hirsch AJ 

PROVIDER: S-EPMC5772047 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Hirsch Alec J AJ   Roberts Victoria H J VHJ   Grigsby Peta L PL   Haese Nicole N   Schabel Matthias C MC   Wang Xiaojie X   Lo Jamie O JO   Liu Zheng Z   Kroenke Christopher D CD   Smith Jessica L JL   Kelleher Meredith M   Broeckel Rebecca R   Kreklywich Craig N CN   Parkins Christopher J CJ   Denton Michael M   Smith Patricia P   DeFilippis Victor V   Messer William W   Nelson Jay A JA   Hennebold Jon D JD   Grafe Marjorie M   Colgin Lois L   Lewis Anne A   Ducore Rebecca R   Swanson Tonya T   Legasse Alfred W AW   Axthelm Michael K MK   MacAllister Rhonda R   Moses Ashlee V AV   Morgan Terry K TK   Frias Antonio E AE   Streblow Daniel N DN  

Nature communications 20180117 1


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-in  ...[more]

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