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Nat Commun. 2018 Jan 17;9(1):263. doi: 10.1038/s41467-017-02499-9.

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

Author information

1
The Vaccine & Gene Institute, Oregon Health and Science University (OHSU), 505 NW 185th Ave, Beaverton, 97006, USA. hirschal@ohsu.edu.
2
Division of Pathobiology & Immunology, Oregon National Primate Research Center (ONPRC), 505 NW 185th Ave, Beaverton, 97006, USA. hirschal@ohsu.edu.
3
Division of Reproductive & Developmental Sciences, ONPRC, 505 NW 185th Ave, Beaverton, 97006, USA.
4
Department of Obstetrics & Gynecology, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
5
The Vaccine & Gene Institute, Oregon Health and Science University (OHSU), 505 NW 185th Ave, Beaverton, 97006, USA.
6
Division of Pathobiology & Immunology, Oregon National Primate Research Center (ONPRC), 505 NW 185th Ave, Beaverton, 97006, USA.
7
Advanced Imaging Research Center, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
8
Utah Center for Advanced Imaging Research, Department of Radiology, University of Utah, 201 President's Circle, Salt Lake City, UT, 84112, USA.
9
Department of Molecular Microbiology & Immunology, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
10
Department of Medicine, Division of Infectious Diseases, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
11
Neuropathology, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
12
Pathology Services Unit, Division of Comparative Medicine, ONPRC, 505 NW 185th Ave, Beaverton, 97006, USA.
13
Clinical Services Unit, Division of Comparative Medicine, ONPRC, 505 NW 185th Ave, Beaverton, 97006, USA.
14
Department of Pathology, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA.
15
Division of Reproductive & Developmental Sciences, ONPRC, 505 NW 185th Ave, Beaverton, 97006, USA. friasa@ohsu.edu.
16
Department of Obstetrics & Gynecology, OHSU, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA. friasa@ohsu.edu.
17
The Vaccine & Gene Institute, Oregon Health and Science University (OHSU), 505 NW 185th Ave, Beaverton, 97006, USA. streblow@ohsu.edu.
18
Division of Pathobiology & Immunology, Oregon National Primate Research Center (ONPRC), 505 NW 185th Ave, Beaverton, 97006, USA. streblow@ohsu.edu.

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.

PMID:
29343712
PMCID:
PMC5772047
DOI:
10.1038/s41467-017-02499-9
[Indexed for MEDLINE]
Free PMC Article

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