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Syncytin-1, syncytin-2 and suppressyn in human health and disease.

ABSTRACT: In this review, we summarized the results of experimental and clinical studies about three human endogenous retroviruses and their products-syncytin-1, syncytin-2, and suppressyn in human physiology and pathophysiology. We summed up the described connection with various pathological processes and diseases, mainly with pregnancy-induced hypertensive diseases such as preeclampsia, oncogenesis, gestational trophoblastic disease, and multiple sclerosis. Supposed mechanisms of action and the potential of clinical applications are also described.

SUBMITTER: Priscakova P

PROVIDER: S-EPMC10697888 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Syncytin-1, syncytin-2 and suppressyn in human health and disease.

Priščáková Petra P Svoboda Michal M Feketová Zuzana Z Hutník Juraj J Repiská Vanda V Gbelcová Helena H Gergely Lajos L

Journal of molecular medicine (Berlin, Germany) 20231019 12

In this review, we summarized the results of experimental and clinical studies about three human endogenous retroviruses and their products-syncytin-1, syncytin-2, and suppressyn in human physiology and pathophysiology. We summed up the described connection with various pathological processes and diseases, mainly with pregnancy-induced hypertensive diseases such as preeclampsia, oncogenesis, gestational trophoblastic disease, and multiple sclerosis. Supposed mechanisms of action and the potentia ...[more]

PMID: 37855856

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Controlling Trophoblast Cell Fusion in the Human Placenta—Transcriptional Regulation of Suppressyn, an Endogenous Inhibitor of Syncytin-1

Project description: Not available

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Endogenous retroviruses Suppressyn and Syncytin-2 as innovative prognostic biomarkers in Acute Myeloid Leukemia.

Project description:IntroductionEmerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood.MethodsIn this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis.ResultsTwo HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis.DiscussionCollectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.

| S-EPMC10808309 | biostudies-literature

Suppressyn localization and dynamic expression patterns in primary human tissues support a physiologic role in human placentation.

Project description:We previously identified suppressyn (SUPYN), a placental protein that negatively regulates the cell fusion essential for trophoblast syncytialization via binding to the trophoblast receptor for syncytin-1, ASCT2, and hypothesized that SUPYN may thereby regulate cell-cell fusion in the placenta. Here, we redefine in vivo SUPYN localization using specific monoclonal antibodies in a rare early placental sample, showing SUPYN localization in villous and extravillous trophoblast subtypes, the decidua and even in placental debris in the maternal vasculature. In human trophoblast cell lines, we show SUPYN alters ASCT2 glycosylation within the secretory pathway and that this binding is associated with inhibition of cell fusion. Using newly-optimized trophoblast isolation protocols that allow tracking of ex vivo cell fusion, we present transcription and translation dynamics of fusion-related proteins over 96 hours in culture and the effects of changes in ambient oxygen levels on these processes. We report converse syncytin-1 and SUPYN transcriptional and translational responses to surrounding oxygen concentrations that suggest both are important in the effects of hypoxia and hyperoxia on placental syncytialization. Our results suggest that SUPYN's anti-fusogenic properties may be exerted at several sites in the maternal body and its dysregulation may be associated with diseases of abnormal placentation.

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Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer 'fossil' in human genome.

Project description:Human endogenous retroviruses (HERVs) are 'fossil viruses' that resulted from stable integrations of exogenous retroviruses throughout evolution. HERVs are defective and do not produce infectious viral particles. However, some HERVs retain a limited coding capacity and produce retroviral transcripts and proteins, which function in human developmental process and various pathologies, including many cancers and neurological diseases. Recently, it has been reported that HERVs are differently expressed in COVID-19 disease caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we discuss the molecular structure and function of HERV ENV proteins, particularly syncytins, and their conventional roles in human development and diseases, and potential involvement in COVID-19 regarding the newly reported mental symptoms. We also address COVID-19 vaccine-related infertility concerns arising from the similarity of syncytin with the spike protein of SARS-CoV-2, which have been proved invalid.

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Could the Human Endogenous Retrovirus-Derived Syncytialization Inhibitor, Suppressyn, Limit Heterotypic Cell Fusion Events in the Decidua?

Project description:Proper placental development relies on tightly regulated trophoblast differentiation and interaction with maternal cells. Human endogenous retroviruses (HERVs) play an integral role in modulating cell fusion events in the trophoblast cells of the developing placenta. Syncytin-1 (ERVW-1) and its receptor, solute-linked carrier family A member 5 (SLC1A5/ASCT2), promote fusion of cytotrophoblast (CTB) cells to generate the multi-nucleated syncytiotrophoblast (STB) layer which is in direct contact with maternal blood. Another HERV-derived protein known as Suppressyn (ERVH48-1/SUPYN) is implicated in anti-fusogenic events as it shares the common receptor with ERVW-1. Here, we explore primary tissue and publicly available datasets to determine the distribution of ERVW-1, ERVH48-1 and SLC1A5 expression at the maternal-fetal interface. While SLC1A5 is broadly expressed in placental and decidual cell types, ERVW-1 and ERVH48-1 are confined to trophoblast cell types. ERVH48-1 displays higher expression levels in CTB and extravillous trophoblast, than in STB, while ERVW-1 is generally highest in STB. We have demonstrated through gene targeting studies that suppressyn has the ability to prevent ERVW-1-induced fusion events in co-culture models of trophoblast cell/maternal endometrial cell interactions. These findings suggest that differential HERV expression is vital to control fusion and anti-fusogenic events in the placenta and consequently, any imbalance or dysregulation in HERV expression may contribute to adverse pregnancy outcomes.

| S-EPMC8508417 | biostudies-literature

Transcriptomic profiling of human gingiva in health and disease

Project description:sc-RNAseq performed on gingival tissue isolated from healthy and periodontitis patients.

2020-12-28 | GSE152042 | GEO

A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2.

Project description:Syncytin-2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD) co-opted by an ancestral primate host, conserved in evolution over >40 Myr, specifically expressed in the placenta, and with a cell-cell fusogenic activity likely contributing to placenta morphogenesis. Here, using the GeneBridge4 human/Chinese hamster radiation hybrid panel, we mapped and identified the human receptor for syncytin-2. This receptor-namely Major Facilitator Superfamily Domain Containing 2 (MFSD2)-belongs to a large family of presumptive carbohydrate transporters with 10-12 membrane-spanning domains, is located at chromosomal position 1p34.2, and is conserved in evolution. An expression vector for MFSD2 confers fusogenicity to otherwise insusceptible cells upon transfection of syncytin-2. It also confers infectivity to syncytin-2 pseudotypes, consistent with this protein being the receptor for the ancestrally acquired HERV-FRD family of endogenous retroviruses. At variance with the human gene, neither mouse nor rat MFSD2 can mediate membrane fusion, which is consistent with the fact that the envelope-derived syncytin genes co-opted by rodents during evolution are not orthologous to the human syncytin genes. Remarkably, a real-time quantitative RT-PCR analysis of MFSD2 in various human tissues demonstrates specific expression in the placenta, as well as in the human BeWo choriocarcinoma cell line, which discloses enhancement of receptor expression upon induction by forskolin of cell-cell fusion and syncytium formation. In situ hybridization of human placental tissue using an MFSD2-specific probe further unambiguously demonstrates receptor expression at the level of the syncytiotrophoblast, again consistent with a role in placenta morphogenesis.

| S-EPMC2582322 | biostudies-literature

Synthesis, assembly, and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope.

Project description:Syncytin is a fusogenic protein involved in the formation of the placental syncytiotrophoblast layer. This protein is encoded by the envelope gene of the ERVWE1 proviral locus belonging to the human endogenous retrovirus W (HERV-W) family. The HERV-W infectious ancestor entered the primate lineage 25 to 40 million years ago. Although the syncytin fusion property has been clearly demonstrated, little is known about this cellular protein maturation process with respect to classical infectious retrovirus envelope proteins. Here we show that the cellular syncytin protein is synthesized as a glycosylated gPr73 precursor cleaved into two mature proteins, a gp50 surface subunit (SU) and a gp24 transmembrane subunit (TM). These SU and TM subunits are found associated as homotrimers. The intracytoplasmic tail is critical to the fusogenic phenotype, although its cleavage requirements seem to have diverged from those of classical retroviral maturation.

| S-EPMC1082723 | biostudies-literature

Plasma proteome profiling to assess human health and disease

Project description:Proteins in the circulatory system mirror an individual´s physiology. They are easy to obtain and consequently, plasma and serum are the predominant matrices for diagnostic analyses in daily clinical practice. Protein levels are generally determined using single protein immuno-assays. Mass spectrometry (MS)-based proteomics of this body fluid is challenging due to the high dynamic range of protein abundances. Here we introduce a rapid and robust single-run proteomic workflow that enables the quantitative analysis of hundreds of plasma proteomes from single finger pricks with 20 min gradients. The apolipoprotein family, inflammatory markers such as C-reactive protein, gender-related proteins and more than 40 FDA approved biomarkers are reproducibly quantified (CV<20% with label-free quantification). Furthermore, we functionally interpret a 1000 protein, quantitative plasma proteome obtained by simple peptide pre-fractionation. ‘Plasma proteome profiling’ delivers an informative portrait of a person’s health state and we envision its large-scale use in biomedicine.

2016-02-22 | PXD002854 | Pride

Human endogenous retroviral syncytin exerts inhibitory effect on invasive phenotype of B16F10 melanoma cells.

Project description:ObjectiveFusogenic endogenous retroviral syncytin plays an important role in the formation of syncytiotrophoblasts in human placenta. Apart from its expression in placenta, brain and testis, syncytin has also been found in many cancers. Although syncytin has been proposed to serve as a positive prognostic marker in some cancers, the underlying mechanism is unclear. The aim of this study is to evaluate the effects of syncytin expression on the invasive phenotype of melanoma cells.MethodsThe eukaryotic expression plasmid for syncytin-EGFP was constructed and transfected into B16F10 melanoma cells. The effect of syncytin on the invasion potential of tumor cells was evaluated in B16F10 subline cells that stably expressed syncytin-EGFP fusion protein or EGFP alone.ResultsThe B16F10 sublines that stably expressed syncytin-EGFP or EGFP alone were established respectively and confirmed by immunofluorescent and immunoblotting assay. Syncytin expression in B16F10 cells was associated with decreased cell proliferation, migration and invasion. Multinucleated giant cells that contained as many as five nuclei were induced in syncytin-expressing cells. In addition, syncytin expression did not alter the sensitivity of B16F10 cells to trichosanthin, a toxin that damages syncytiotrophoblasts more efficiently than other tissues.ConclusionsThese results suggest that syncytin expression in some cancers may confine their invasion potential and thus serve as a positive prognostic factor.

| S-EPMC3828447 | biostudies-literature

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