The role of human endogenous retrovirus (HERV)-K env in THP-1 monocytic cell differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE240644 | GEO | 2024/08/01
REPOSITORIES: GEO
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Project description:Human Endogenous Retroviruses (HERVs) are exogenous viral elements that integrated into the germline millions of years ago. They comprise 8% of the human genome and play a critical role in cellular differentiation during development. HERV-K(HML-2) is the most recently integrated and actively transcribed HERV. It is found to be highly expressed in pluripotent stem cells and strongly downregulated during cellular differentiation. Moreover, expression of HERV-K in terminally differentiated neurons results in cytotoxicity. Expression of HERVs has been implicated in carcinogenesis and is suggested to confer stem cell like features important for cell growth. Atypical Teratoid / Rhabdoid Tumor (AT/RT) is a rare pediatric brain cancer that results from incomplete neuronal differentiation during embryonic development. In this paper, we investigated the cytopathic effect of Ouabain, a cardiac glycoside that induces cytotoxicity in stem cells, on AT/RT cells. We characterized four AT/RT cell lines by immunostaining and observed variable levels of stem cell, Oct4 and Pax6, and neuronal differentiation markers, TUBB3 and MAP2, as well as HERV-K envelope (env), polymerase (pol), and gag transcripts. We stained formalin-fixed brain tissues from 20 AT/RT patients and 5 unaffected controls for HERV-K ENV protein expression. 40% of AT/RT patient tissues showed ENV expression. In contrast, no ENV immunostaining was observed in all 5 control brain tissues. We used Ouabain, known to be cytotoxic to stem cells, observed up to 50% toxicity at 24 hr and 80% toxicity at 48 hr after treatment. While AT/RT primarily exist as large cell aggregates in suspension, Ouabain treatment downregulated HERV-K ENV protein and caused disruption of cell-to-cell interactions. Similarly, when AT/RT cells were transfected with a CRISPR/Cas9 construct designed to repress HERV-K promotor activity, cell aggregates separated and cell viability decreased significantly. Using a luciferase reporter construct under the control of a HERV-K promotor, we observed a significant decrease in HERV-K promotor activity at 8 to 72 hr post treatment with 0.5 uM Ouabain. Given that downregulation of HERV-K alone was sufficient to cause cytotoxicity in the cells, HERV-K expression may be essential for AT/RT growth and survival. Ouabain and other compounds that modulate HERV expression may provide an alternative or adjunctive therapeutic option for treatment of embryonal tumors.
2021-06-28 | GSE124210 | GEO
Project description:The endogenous retrovirus type W (HERV-W) is a human specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex vivo, given the human specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify a HERV-W specific signature in glial cells, the current study analyzed the transcriptome of ENV stimulated microglial- and astroglial cells and compared the transcriptomic signature to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.
2024-03-30 | GSE262029 | GEO
Project description:Human endogenous retrovirus (HERV) genes were incorporated into the genome over millions of years but they mostly have inactivating mutations. HERV-K is the most recently incorporated virus. Incidental HERV-K gene expression occurs in a variety of pathological conditions. However, its physiological role is poorly understood. To study the role of HERV-K in development, we monitored its expression and function in pluripotent stem cells and during the process of neuronal differentiation. The expression of HERV-K env was localized to chromosomes 12 and 19. HERV-K Env was expressed on the cell surface of pluripotent stem cells and was critical in maintaining the stemness and adhesion of the cells. Interactions with CD98HC resulted in activation of signaling pathways that regulate stem cells genes. Down regulation of HERV-K env resulted in dissociation of the stem cell colonies and enhanced differentiation along neuronal pathways. HERV-K env expression during neurodevelopment was regulated by DNA methylation. Thus HERV-K regulation is critical for human embryonic and neurodevelopment.
2020-08-05 | GSE110267 | GEO
Project description:Human endogenous retrovirus (HERV) genes were incorporated into the genome over millions of years but they mostly have inactivating mutations. HERV-K is the most recently incorporated virus. Incidental HERV-K gene expression occurs in a variety of pathological conditions. However, its physiological role is poorly understood. To study the role of HERV-K in development, we monitored its expression and function in pluripotent stem cells and during the process of neuronal differentiation. The expression of HERV-K env was localized to chromosomes 12 and 19. HERV-K Env was expressed on the cell surface of pluripotent stem cells and was critical in maintaining the stemness and adhesion of the cells. Interactions with CD98HC resulted in activation of signaling pathways that regulate stem cells genes. Down regulation of HERV-K env resulted in dissociation of the stem cell colonies and enhanced differentiation along neuronal pathways. HERV-K env expression during neurodevelopment was regulated by DNA methylation. Thus, HERV-K regulation is critical for human embryonic and neurodevelopment.
2020-08-05 | GSE110497 | GEO
Project description:This project seeks to identify protein-protein interactions with human endogenous retrovirus K envelope protein. A flag-tagged HERV-K env construct (fHERV-K env) was expressed in HEK293 cells. An anti-flag MAb was immobilized on magnetic protein G beads was used to capture fHERV-K env and interactors.
2020-07-06 | PXD019702 | Pride
Project description:A proteome comparison was performed to assess the responses of human monocytic cells (THP-1) to gold-nanoparticles (Au-NPs) of two different diameter sizes (5 or 20 nm) with different surface functional groups, i.e., alkylammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated thiolate Au-NPs.
2019-03-18 | PXD010858 | Pride
Project description:Streptococcus suis is an important zoonosis pathogen that causes significant economic losses worldwide characterized by meningitis, septicaemia, arthritis, bronchopneumonia endocarditis. Streptcoccus suis 2 strain SC19 was isolated in Sichuan province in China, during the outbreak in 2005. Septicemia is most popular symptoms for SC19 infection, and mortality is high. We used human acute monocytic leukemia cell line (THP-1) infected SC19 to analysis the pathomechanism of septicemia in SS2 infection. Human acute monocytic leukemia cell line (THP-1) cells were stimulated with Streptcoccus suis 2 (SS2) strain SC19. We added SS2 to THP-1 cells at a MOI of 1:1 (bacteria/cells). Uninfected control cells were incubated with PBS only. After 3 hours incubation, cells were collected for RNA extraction and hybridization on Affymetrix microarrays. A total of 4 samples were challenged, and 4 samples were used as controls. 4 microarrays were used in this experiment.
2010-04-06 | E-GEOD-20508 | biostudies-arrayexpress
Project description:Transcriptome comparison to assess the responses of human monocytic cells (THP-1) to gold-nanoparticles (Au-NPs) of two different diameter sizes (5 or 20 nm) with different surface functional groups, i.e., alkylammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated thiolate Au-NPs.
2019-06-04 | E-MTAB-7093 | biostudies-arrayexpress
Project description:HERV-K ENV expression is a therapeutic target in atypical teratoid rhabdoid tumors
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2021-09-06 | GSE157514 | GEO