Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

Abstract Zika virus (ZIKV) infection at the maternal–placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentia...

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Main Authors: Lindsey N. Block, Jenna Kropp Schmidt, Nicholas S. Keuler, Megan C. McKeon, Brittany D. Bowman, Gregory J. Wiepz, Thaddeus G. Golos
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-11275-9
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author Lindsey N. Block
Jenna Kropp Schmidt
Nicholas S. Keuler
Megan C. McKeon
Brittany D. Bowman
Gregory J. Wiepz
Thaddeus G. Golos
author_facet Lindsey N. Block
Jenna Kropp Schmidt
Nicholas S. Keuler
Megan C. McKeon
Brittany D. Bowman
Gregory J. Wiepz
Thaddeus G. Golos
author_sort Lindsey N. Block
collection DOAJ
description Abstract Zika virus (ZIKV) infection at the maternal–placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) mRNA, miRNA and protein cargo, including ZIKV proteins, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.
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spelling doaj.art-655af951117f40ff939cf220e7760d372022-12-22T02:53:53ZengNature PortfolioScientific Reports2045-23222022-05-0112112010.1038/s41598-022-11275-9Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblastsLindsey N. Block0Jenna Kropp Schmidt1Nicholas S. Keuler2Megan C. McKeon3Brittany D. Bowman4Gregory J. Wiepz5Thaddeus G. Golos6Wisconsin National Primate Research Center, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonDepartment of Statistics, University of Wisconsin-MadisonDepartment of Biomolecular Chemistry, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonAbstract Zika virus (ZIKV) infection at the maternal–placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) mRNA, miRNA and protein cargo, including ZIKV proteins, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.https://doi.org/10.1038/s41598-022-11275-9
spellingShingle Lindsey N. Block
Jenna Kropp Schmidt
Nicholas S. Keuler
Megan C. McKeon
Brittany D. Bowman
Gregory J. Wiepz
Thaddeus G. Golos
Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
Scientific Reports
title Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
title_full Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
title_fullStr Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
title_full_unstemmed Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
title_short Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
title_sort zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts
url https://doi.org/10.1038/s41598-022-11275-9
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