Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences

2010 ◽  
Vol 41 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Pornrutsami Jintaridth ◽  
Apiwat Mutirangura
Keyword(s):  
Mononuclear Cells ◽  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cellular Functions ◽  
Peripheral Blood Mononuclear ◽  
Global Methylation ◽  
Short Interspersed Elements ◽  
Genome Wide ◽  
Age Dependent

Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = −0.452, P < 10−3) and HERV-K (r = −0.326, P < 10−3) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34–68 yr, and loss of methylation of HERV-K occurred during ages 40–63 yr and again during ages 64–83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10−3). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

scholarly journals Virome Sequencing in Patients With Myocarditis

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Bettina Heidecker ◽  
Simon H. Williams ◽  
Komal Jain ◽  
Alexandra Oleynik ◽  
Dimitri Patriki ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Cardiac Tissue ◽  
Mononuclear Cells ◽  
Endogenous Retrovirus ◽  
Fulminant Myocarditis ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Cardiac Tissues ◽  
Barr Virus

Background: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. Methods: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). Results: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. Conclusions: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.

scholarly journals Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells

2020 ◽  
Vol 8 (9) ◽  
pp. 1335
Author(s):  
Arthur Dechaumes ◽  
Antoine Bertin ◽  
Famara Sane ◽  
Sandrine Levet ◽  
Jennifer Varghese ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Mrna Level ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Enteroviral Infection ◽  
Coxsackievirus B4 ◽  
Ductal Cells ◽  
Pancreatic Ductal Cells ◽  
Pancreatic Cells

Human Endogenous Retrovirus W Envelope (HERV-W ENV) mRNA or protein can be found in peripheral blood mononuclear cells (PBMCs) and exocrine pancreas of patients with type 1 diabetes (T1D). Further, previous observations have shown an association between enteroviral infection and development of T1D; specifically, coxsackievirus-B (CV-B) has been detected in the blood and pancreas of patients with T1D. Notably, viruses can activate HERV-W expression. Hence, we evaluated the effect of CV-B4 infection on HERV-W ENV mRNA expression. Primary human pancreatic ductal cells were obtained from five brain-dead donors. In the pancreatic cells of three donors, the HERV-W ENV mRNA level measured using RT-qPCR was upregulated upon CV-B4 infection. The HERV-W ENV protein was detected in the infected cells using the immunoblot assay. In human PBMCs inoculated with CV-B4 or when CV-B4 was incubated with an enhancing serum, the HERV-W ENV mRNA level was higher than the background RNA level. In monocyte-derived macrophages obtained from 5 of 13 donors, the HERV-W ENV mRNA level was higher in cultures inoculated with CV-B4 than in the control. Therefore, CV-B4 can upregulate or induce the transcription of a certain HERV-W ENV copy (or copies) in primary cell cultures, such as monocytes, macrophages, and pancreatic cells.

scholarly journals THE COMPARATIVE STUDY OF HUMAN ENDOGENOUS RETROVIRUS HERV-E λ 4-1 EXPRESSION IN BLOOD IMMUNE CELLS OF MULTIPLE SCLEROSIS PATIENTS

2019 ◽  
Vol 19 (1S) ◽  
pp. 78-80
Author(s):  
I A Goldina ◽  
E V Markova
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Endogenous Retrovirus ◽  
Pokeweed Mitogen ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Multiple Sclerosis Patients

In order to investigate the function of human endogenous retrovirus HERV-E λ 4-1 in multiple sclerosis pathogenesis, the comparative research of frequency of this retrovirus expression and mRNA level on different types of blood immune cells of progredient course multiple sclerosis patients have been conducted with using of the reverse - transcriptase polymerase chain reaction method. Peripheral blood mononuclear cells were isolated on Ficoll density gradient centrifugations. Monocytes were separated by the adhesion to plastic Petri dishes. For the estimation of the mitogen-induced HERV-E λ 4-1 expression, blood mononuclear cells were incubated with adding of phytogemagglutinin or pokeweed mitogen during 72 hours in CO2 incubator at 37 °C and 5% CO2. Results of HERV-E λ 4-1 env gene expression estimation demonstrate that both monocytes and lymphocytes express HERV-E λ 4-1. The level of the HERV-E λ 4-1 env mRNA was higher in lymphocytes than in monocytes. The main source of HERV-E λ 4-1 in progredient course MS patients between blood immune cells are lymphocytes, especially B lymphocytes.

scholarly journals The Decrease in Human Endogenous Retrovirus-H Activity Runs in Parallel with Improvement in ADHD Symptoms in Patients Undergoing Methylphenidate Therapy

2018 ◽  
Vol 19 (11) ◽  
pp. 3286 ◽  
Author(s):  
Cipriani Chiara ◽  
Pitzianti Bernanda ◽  
Matteucci Claudia ◽  
D’Agati Elisa ◽  
Miele Tony ◽  
...  
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Dynamic Regulation ◽  
Expression Levels

Increasing scientific evidence demonstrated the deregulation of human endogenous retroviruses (HERVs) expression in complex diseases, such as cancer, autoimmune, psychiatric, and neurological disorders. The dynamic regulation of HERV activity and their responsiveness to a variety of environmental stimuli designate HERVs as genetic elements that could be modulated by drugs. Methylphenidate (MPH) is widely used in the treatment of attention deficit hyperactivity disorder (ADHD). The aim of this study was to evaluate the time course of human endogenous retrovirus H (HERV-H) expression in peripheral blood mononuclear cells (PBMCs) with respect to clinical response in ADHD patients undergoing MPH therapy. A fast reduction in HERV-H activity in ADHD patients undergoing MPH therapy was observed in parallel with an improvement in clinical symptoms. Moreover, when PBMCs from drug-naïve patients were cultured in vitro, HERV-H expression increased, while no changes in the expression levels were found in ADHD patients undergoing therapy. This suggests that MPH could affect the HERV-H activity and supports the hypothesis that high expression levels of HERV-H could be considered a distinctive trait of ADHD patients.

scholarly journals Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†

2019 ◽  
Author(s):  
Adjimon G Lokossou ◽  
Caroline Toudic ◽  
Phuong Trang Nguyen ◽  
Xavier Elisseeff ◽  
Amandine Vargas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Map Kinases ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Endogenous Retrovirus ◽  
Jurkat Cells ◽  
Peripheral Blood Mononuclear ◽  
Interfering Rna

Abstract Modulation of the activation status of immune cell populations during pregnancy depends on placental villous cytotrophoblast (VCT) cells and the syncytiotrophoblast (STB). Failure in the establishment of this immunoregulatory function leads to pregnancy complications. Our laboratory has been studying Syncytin-2 (Syn-2), an endogenous retroviral protein expressed in placenta and on the surface of placental exosomes. This protein plays an important role not only in STB formation through its fusogenic properties, but also through its immunosuppressive domain (ISD). Considering that Syn-2 expression is importantly reduced in preeclamptic placentas, we were interested in addressing its possible immunoregulatory effects on T cells. Activated Jurkat T cells and peripheral blood mononuclear cells (PBMCs) were treated with monomeric or dimerized version of a control or a Syn-2 ISD peptide. Change in phosphorylation levels of ERK1/2 MAP kinases was selectively noted in Jurkat cells treated with the dimerized ISD peptide. Upon incubation with the dimerized Syn-2 ISD peptide, significant reduction in Th1 cytokine production was further demonstrated by ELISA and Human Th1/Th2 Panel Multi-Analyte Flow Assay. To determine if exosome-associated Syn-2 could also be immunosuppressive placental exosomes were incubated with activated Jurkat and PBMCs. Quantification of Th1 cytokines in the supernatants revealed severe reduction in T cell activation. Interestingly, exosomes from Syn-2-silenced VCT incubated with PBMCs were less suppressive when compared with exosome derived from VCT transfected with control small interfering RNA (siRNA). Our results suggest that Syn-2 is an important immune regulator both locally and systemically, via its association with placental exosomes.

scholarly journals Single-dose MGTA-145/plerixafor leads to efficient mobilization and in vivo transduction of HSCs with thalassemia correction in mice

2021 ◽  
Vol 5 (5) ◽  
pp. 1239-1249
Author(s):  
Chang Li ◽  
Kevin A. Goncalves ◽  
Tamás Raskó ◽  
Amit Pande ◽  
Sucheol Gil ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mononuclear Cells ◽  
Vector System ◽  
Hemopoietic Stem Cell ◽  
Peripheral Blood Mononuclear ◽  
Gene Therapy Approach ◽  
Vector Integration ◽  
Genome Wide ◽  
Gfp Marking

Abstract We have developed an in vivo hemopoietic stem cell (HSC) gene therapy approach without the need for myelosuppressive conditioning and autologous HSC transplantation. It involves HSC mobilization and IV injection of a helper-dependent adenovirus HDAd5/35++ vector system. The current mobilization regimen consists of granulocyte colony-stimulating factor (G-CSF) injections over a 4-day period, followed by the administration of plerixafor/AMD3100. We tested a simpler, 2-hour, G-CSF–free mobilization regimen using truncated GRO-β (MGTA-145; a CXCR2 agonist) and plerixafor in the context of in vivo HSC transduction in mice. The MGTA-145+plerixafor combination resulted in robust mobilization of HSCs. Importantly, compared with G-CSF+plerixafor, MGTA-145+plerixafor led to significantly less leukocytosis and no elevation of serum interleukin-6 levels and was thus likely to be less toxic. With both mobilization regimens, after in vivo selection with O6-benzylguanine (O6BG)/BCNU, stable GFP marking was achieved in &gt;90% of peripheral blood mononuclear cells. Genome-wide analysis showed random, multiclonal vector integration. In vivo HSC transduction after mobilization with MGTA-145+plerixafor in a mouse model for thalassemia resulted in &gt;95% human γ-globin+ erythrocytes at a level of 36% of mouse β-globin. Phenotypic analyses showed a complete correction of thalassemia. The γ-globin marking percentage and level were maintained in secondary recipients, further demonstrating that MGTA145+plerixafor mobilizes long-term repopulating HSCs. Our study indicates that brief exposure to MGTA-145+plerixafor may be advantageous as a mobilization regimen for in vivo HSC gene therapy applications across diseases, including thalassemia and sickle cell disease.

scholarly journals Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

2018 ◽  
Vol 45 (5) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haiqiang Yao ◽  
Shanlan Mo ◽  
Ji Wang ◽  
Yingshuai Li ◽  
Chong-Zhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metabolic Disorders ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Body Type ◽  
Peripheral Blood Mononuclear ◽  
Molecular Features ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

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