Smoking Increases Transcription of Human Endogenous Retroviruses in a Newly Established in Vitro Cell Model and in Normal Urothelium

2010 ◽  
Vol 26 (8) ◽  
pp. 883-888 ◽  
Author(s):  
Ute Gabriel ◽  
Annette Steidler ◽  
Lutz Trojan ◽  
Maurice Stephan Michel ◽  
Wolfgang Seifarth ◽  
...  
Keyword(s):  
Cell Model ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Normal Urothelium

scholarly journals Ancient Adversary – HERV-K (HML-2) in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Eoin Dervan ◽  
Dibyangana D. Bhattacharyya ◽  
Jake D. McAuliffe ◽  
Faizan H. Khan ◽  
Sharon A. Glynn
Keyword(s):  
Tumour Progression ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Human Endogenous Retroviruses ◽  
Viral Particles ◽  
Metastatic Capacity ◽  
Coding Capacity ◽  
Reading Frames

Human endogenous retroviruses (HERV), ancient integrations of exogenous viruses, make up 8% of our genome. Long thought of as mere vestigial genetic elements, evidence is now accumulating to suggest a potential functional role in numerous pathologies including neurodegenerative diseases, autoimmune disorders, and multiple cancers. The youngest member of this group of transposable elements is HERV-K (HML-2). Like the majority of HERV sequences, significant post-insertional mutations have disarmed HERV-K (HML-2), preventing it from producing infectious viral particles. However, some insertions have retained limited coding capacity, and complete open reading frames for all its constituent proteins can be found throughout the genome. For this reason HERV-K (HML-2) has garnered more attention than its peers. The tight epigenetic control thought to suppress expression in healthy tissue is lost during carcinogenesis. Upregulation of HERV-K (HML-2) derived mRNA and protein has been reported in a variety of solid and liquid tumour types, and while causality has yet to be established, progressively more data are emerging to suggest this phenomenon may contribute to tumour growth and metastatic capacity. Herein we discuss its potential utility as a diagnostic tool and therapeutic target in light of the current in vitro, in vivo and clinical evidence linking HERV-K (HML-2) to tumour progression.

RNAseq analysis to identify functional products derived from human endogenous retroviruses in in-vitro syncytialization model

Placenta ◽  
2016 ◽  
Vol 46 ◽  
pp. 106
Author(s):  
Kazuki Morita ◽  
Takeshi Nagamatsu ◽  
So Nakagawa ◽  
Jun Sugimoto ◽  
Kei Kawana ◽  
...  
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses

scholarly journals Structural basis for Fullerene geometry in a human endogenous retrovirus capsid

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Oliver Acton ◽  
Tim Grant ◽  
Giuseppe Nicastro ◽  
Neil J. Ball ◽  
David C. Goldstone ◽  
...  
Keyword(s):  
Early Stage ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Structural Basis ◽  
Human Endogenous Retrovirus ◽  
Structural Protein ◽  
Human Endogenous Retroviruses ◽  
Reading Frames

AbstractThe HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency as well as inflammatory disease, cancers and HIV-1 infection. Here, we reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies. These icosahedral and capsular assemblies reveal at high-resolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores.

scholarly journals HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 145
Author(s):  
Qiujin Yan ◽  
Xiulin Wu ◽  
Ping Zhou ◽  
Yan Zhou ◽  
Xuhang Li ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Direct Interaction ◽  
Endogenous Retroviruses ◽  
Sodium Influx ◽  
Human Endogenous Retroviruses ◽  
Whole Cell Patch Clamp ◽  
Laser Confocal Scanning Microscopy ◽  
Confocal Scanning ◽  
Confocal Scanning Microscopy

An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.

scholarly journals Human endogenous retroviruses and multiple sclerosis: Causation, association, or after-effect?

2017 ◽  
Vol 23 (8) ◽  
pp. 1050-1055 ◽  
Author(s):  
Elena Morandi ◽  
Rachael E. Tarlinton ◽  
Radu Tanasescu ◽  
Bruno Gran
Keyword(s):  
Experimental Studies ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Human Endogenous Retroviruses ◽  
Immune Mediated ◽  
After Effect ◽  
Possible Cause

From the early days of MS discovery, infections have been proposed as a possible cause of the disease. In the last three decades, an association between human endogenous retrovirus expression and MS has been further investigated and confirmed. Nevertheless, the role of such retroviruses in the disease needs clarification. In this review, we introduce MSRV/HERV-W and describe its association with MS. We then summarize the evidence for the involvement of MSRV/HERV-W in the aetiology and progression of MS and its possible role as biomarker and drug target. Biological mechanisms for HERV effects in MS may involve the activation of innate immune pathways by the envelope protein of MSRV (MSRVEnv). In addition to in vitro and experimental studies, further insight on how HERVs may influence immune-mediated pathology in MS may also come from the use of antiretroviral treatments in patients.

scholarly journals Infection by Diverse HIV-1 Subtypes Leads to Different Elevations in HERV-K Transcriptional Levels in Human T Cell Lines

2021 ◽  
Vol 12 ◽  
Author(s):  
Xi Li ◽  
Yaolin Guo ◽  
Hanping Li ◽  
Xiaofeng Huang ◽  
Zhichao Pei ◽  
...  
Keyword(s):  
The Body ◽  
Endogenous Retroviruses ◽  
Tat Protein ◽  
Biological Regulation ◽  
Human Endogenous Retroviruses ◽  
Human T Cell ◽  
Significant Difference ◽  
T Cell Lines ◽  
Hiv 1

Human endogenous retroviruses (HERVs) make up ~8% of the human genome, and for millions of years, they have been subject to strict biological regulation. Many HERVs do not participate in normal physiological activities in the body. However, in some pathological conditions, they can be abnormally activated. For example, HIV infection can cause abnormal activation of HERVs, and under different infection conditions, HERV expression may be different. We observed significant differences in HERV-K transcription levels among HIV-1 subtype-infected individuals. The transcriptional levels in the HERV-K gag region were significantly increased in HIV-1 B subtype-infected patients, while the transcriptional levels in the HERV-K pol region were significantly increased in CRF01_AE and CRF07_BC subtype-infected patients. In vitro, the transcriptional levels of HEVR-K were increased 5-fold and 15-fold in MT2 cells transfected with two different HIV-1 strains (B and CRF01_AE, respectively). However, there was no significant difference in transcriptional levels among regions of HERV-K. When MT2 cells were infected with different subtypes of HIV-1 Tat proteins (B, CRF01_AE), which is constructed by lentiviruses, and the transcription levels of HERV-K were increased 4-fold and 2-fold, respectively. Thus, different subtypes of HIV-1 have different effects on HERV-K transcription levels, which may be caused by many factors, not only Tat protein.

scholarly journals HIV-1 Infection Increases the Expression of Human Endogenous Retroviruses Type K (HERV-K)in Vitro

2007 ◽  
Vol 23 (1) ◽  
pp. 116-122 ◽  
Author(s):  
Rafael Contreras-Galindo ◽  
Pablo López ◽  
Rosa Vélez ◽  
Yasuhiro Yamamura
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Type K ◽  
Hiv 1

scholarly journals The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

2018 ◽  
Vol 24 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Antonina Dolei
Keyword(s):  
Multiple Sclerosis ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Barr Virus ◽  
Phase Ii Clinical Trials ◽  
Epstein Barr

Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance. Effective anti-MS therapies strongly reduced MSRV/Syncytin-1/HERV-W expression. The Epstein–Barr virus (EBV) activates HERV-W/MSRV in vitro and in vivo, in patients with infectious mononucleosis and controls with high anti-EBNA1-IgG titers. Thus, the two main EBV/MS links (infectious mononucleosis and high anti-EBNA1-IgG titers) are paralleled by activation of HERV-W/MSRV. It is hypothesized that EBV may act as initial trigger of future MS, years later, by activating MSRV, which would act as direct neuropathogenic effector, before and during MS.

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

Expression of human endogenous retroviruses and associated transcripts in Hodgkin lymphoma cells

2020 ◽  
Author(s):  
K Engel ◽  
A Krüger ◽  
V Vandrey ◽  
J Schneider ◽  
I Volkmer ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Endogenous Retroviruses ◽  
Lymphoma Cells ◽  
Human Endogenous Retroviruses
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