Transcriptomics analysis of trimester-specific full-term placentas from three Zika virus-infected women
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139181 | GEO | 2019/10/22
REPOSITORIES: GEO
Similar Datasets
Project description:Zika virus (ZIKV) compromises the placental integrity infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection, are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in inflammation. The purpose of this work iis work aims to investigate CSTB, RAGE, and AXL receptor expression in ZIKV infected placental tissues at term. The hypothesis is that in ZIKV-infected placenta, there is overexpression of CSTB and increased inflammation affecting the RAGE and AXL receptor expression. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and Western Blot analysis were performed to analyze proteins and pathways affected by ZIKV infection in frozen placenta. Pathological The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblasts layer, and cell agglutination associated to with ZIKV infection of placental tissue. ZIKV infection was mostly localized to the trophoblast layer. There was a significant decrease in the expression of CSTB, RAGE and AXLCSTB, RAGE and AXL expression in ZIKV positive placenta. This downregulation can impair immune responses and facilitate virus penetration into the placenta. Results are consistent with our previous studies and literature of on ZIKV infection by activation ofng Inflammasome and Pyroptosis through caspase 1 upregulation and affecting the cellular structure, tissue remodeling, and cell differentiation by upregulation of tubulin beta and heat shock protein 27.
2023-03-11 | PXD037388 | Pride
Project description: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) protein, mRNA, and miRNA cargo, 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.
2022-05-20 | PXD033289 | Pride
Project description:Zika Virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity. Flavivirus have shown deregulation of the host proteome, specially extracellular matrix (ECM) proteins. Our hypothesis is that ZIKV infection of placental tissue deregulates specific ECM proteome, allowing a mechanism of persistent infection and loss of placental integrity. Using nine different placental samples from Puerto Rico collected during 2016 ZIKV epidemic, we compared the proteome of five ZIKV infected samples with uninfected controls. Quantitative proteomics was performed using tandem mass tag TMT10plex™ Isobaric Label Reagent Set followed by Q Exactive™ Hybrid Quadrupole Orbitrap Mass Spectrometry. Identification of proteins was performed by Proteome Discover 2.1, and protein fold change in both groups was compared using Limma software. Differentially expressed proteins were analyzed with STRING and Ingenuity Pathway using both the fold change and p-value. TMT analysis showed that ZIKV infected placentas had 94 reviewed differentially abundant proteins, 32 More abundant and 62 Less abundant. STRING analysis results indicate that 45 of the deregulated proteins are cellular components of the ECM and 16 play a role in its structure and organization. Some of the significantly More abundant proteins were Fibrinogen, Vitronectin and Fibronectin. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of the mechanism (s) employed by ZIKV during placental infection and give insight on novel targets used to disrupt placental function.
2022-06-09 | PXD023964 | Pride
Project description: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 directed to differentiate 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) protein, mRNA, and miRNA cargo, 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.
2022-01-01 | GSE185291 | GEO
Project description: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 directed to differentiate 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) protein, mRNA, and miRNA cargo, 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.
2022-01-10 | GSE193195 | GEO
Project description:Zika virus (ZIKV) infection during pregnancy results in an increased risk of spontaneous abortion and vertical transmission across placenta results in severe congenital defects in newborns. While the infectivity and pathological effects of ZIKV on the placental trophoblast progenitor cells in early human embryos remains largely unknown. Here, using the human trophoblast stem cells (hTSCs) isolated from human blastocyst, we showed that hTSCs were permissive to ZIKV infection, while resistance to ZIKV increased with differentiation. Combined CRISPR/Cas9-mediated gene knockout and RNA-seq assays, we demonstrated that the intrinsic expression of AXL and TIM-1, as well as the absence of potent interferon (IFN)-stimulated genes (ISGs), contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived 3 dimensional (3D) placental trophoblast organoid model, we demonstrated that ZIKV infection completely disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Overall, our results clearly demonstrated that hTSCs represented the major target cells of ZIKV, and a possible reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepened our understanding of the characteristics and consequences of ZIKV infection of trophoblast stem cells in early human embryo.
2023-08-03 | GSE229702 | GEO
Project description:We and others have demonstrated Zika virus (ZIKV) congenital infection evades double-stranded RNA detection, and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. We used orthogonal approaches to test the hypothesis that ZIKV disrupts placental miRNAs to enable viral persistence and fetal pathogenesis. In primary human trophoblasts, high-throughput sequencing crosslinking and immunoprecipitation (AGO-HITS-CLIP) demonstrated an unexpected disruption of placental miRNA-regulated TGF-β networks. In gnotobiotic mice, absence of microbes rendered normally resistant mice susceptible to congenital ZIKV infection, and placental spatial transcriptomics revealed distinct microenvironments defined by significant upregulation of complement cascade components. Finally, treatment of ZIKV-infected mice with the RNAi-enhancer enoxacin led to loss of ZIKV placental persistence and rescue of fetal growth restriction. These results collectively suggest that ZIKV co-opts miRNA inflammatory regulatory networks to persist in the placenta reservoir, a conduit of vertical transmission and fetal pathogenesis.
2023-06-03 | GSE205609 | GEO
Project description:We and others have demonstrated Zika virus (ZIKV) congenital infection evades double-stranded RNA detection, and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. We used orthogonal approaches to test the hypothesis that ZIKV disrupts placental miRNAs to enable viral persistence and fetal pathogenesis. In primary human trophoblasts, high-throughput sequencing crosslinking and immunoprecipitation (AGO-HITS-CLIP) demonstrated an unexpected disruption of placental miRNA-regulated TGF-β networks. In gnotobiotic mice, absence of microbes rendered normally resistant mice susceptible to congenital ZIKV infection, and placental spatial transcriptomics revealed distinct microenvironments defined by significant upregulation of complement cascade components. Finally, treatment of ZIKV-infected mice with the RNAi-enhancer enoxacin led to loss of ZIKV placental persistence and rescue of fetal growth restriction. These results collectively suggest that ZIKV co-opts miRNA inflammatory regulatory networks to persist in the placenta reservoir, a conduit of vertical transmission and fetal pathogenesis.
2023-06-03 | GSE205631 | GEO
Project description:Zika virus (ZIKV) infection has caused severe unexpected clinical outcomes in neonates and adults during the recent outbreak in Latin America, particularly in Brazil. Congenital malformations associated with ZIKV have been frequently reported; nevertheless, the mechanism of vertical transmission and the involvement of placental cells remains unclear. In this study, we applied quantitative proteomics analysis in a floating explant model of chorionic villi of human placental tissues incubated with ZIKV and with ZIKV pre-adsorbed with anti-ZIKV envelope protein. The regulation of specific proteins was measured using immunofluorescence and immunoperoxidase assays. Altered levels of proteins were involved in cell proliferation, apoptosis, inflammatory processes, and the integrin-cytoskeleton complex. Antibody-opsonized ZIKV particles differentially modulated the pattern of protein expression in placental cells; this phenomenon may play a pivotal role in determining the course of infection and the role of mixed infections. These data fill gaps in our understanding of ZIKV in the placenta and help identify infection control targets.
2021-12-30 | PXD025764 | Pride
Project description:Blood CD14+ monocytes are the frontline immunomodulators categorized into classical, intermediate or non-classical subsets, subsequently differentiating into M1 pro- or M2 anti-inflammatory macrophages upon stimulation. While Zika virus (ZIKV) rapidly establishes viremia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by Asian-lineage ZIKV infection. Importantly, infection of pregnant women’s blood revealed enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women’s blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with global suppression of type I interferon-signaling pathway and an aberrant expression of host genes associated with pregnancy complications. 30 ZIKV+ sera from symptomatic pregnant patients also showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, upon infection with different lineages of ZIKV.
2017-08-14 | GSE101718 | GEO