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 Detection and Characterization of Porcine Endogenous Retrovirus in Porcine Plasma and Porcine Factor VIII

2001 ◽  
Vol 75 (10) ◽  
pp. 4551-4557 ◽  
Author(s):  
Daniel M. Takefman ◽  
Susan Wong ◽  
Thomas Maudru ◽  
Keith Peden ◽  
Carolyn A. Wilson
Keyword(s):  
Factor Viii ◽  
Mononuclear Cells ◽  
Infectious Virus ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Peripheral Blood Mononuclear ◽  
Porcine Endogenous Retrovirus ◽  
Pig Genome

ABSTRACT The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo.

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 Identification of Exogenous Forms of Human-Tropic Porcine Endogenous Retrovirus in Miniature Swine

2004 ◽  
Vol 78 (5) ◽  
pp. 2494-2501 ◽  
Author(s):  
James C. Wood ◽  
Gary Quinn ◽  
Kristen M. Suling ◽  
Beth A. Oldmixon ◽  
Brian A. Van Tine ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Germ Line ◽  
Endogenous Retrovirus ◽  
Human Cells ◽  
Miniature Swine ◽  
Peripheral Blood Mononuclear ◽  
Infectious Risk ◽  
Porcine Endogenous Retrovirus ◽  
Principal Source

ABSTRACT The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B in certain human cell lines indicates that PERV may pose an infectious risk in clinical xenotransplantation. We have previously reported that human-tropic PERVs isolated from infected human cells following cocultivation with miniature swine peripheral blood mononuclear cells (PBMC) are recombinants of PERV-A with PERV-C. Here, we report that these recombinants are exogenous viruses in miniature swine; i.e., they are not present in the germ line DNA. These viruses were invariably present in miniature swine that transmitted PERV to human cells and were also identified in some miniature swine that lacked this ability. These data, together with the demonstration of the absence of both replication-competent PERV-A and recombinant PERV-A/C loci in the genome of miniature swine (L. Scobie, S. Taylor, J. C. Wood, K. M. Suling, G. Quinn, C. Patience, H.-J. Schuurman, and D. E. Onions, J. Virol. 78:2502-2509, 2004), indicate that exogenous PERV is the principal source of human-tropic virus in these animals. Interestingly, strong expression of PERV-C in PBMC correlated with an ability of the PBMC to transmit PERV-A/C recombinants in vitro, indicating that PERV-C may be an important factor affecting the production of human-tropic PERV. In light of these observations, the safety of clinical xenotransplantation from miniature swine will be most enhanced by the utilization of source animals that do not transmit PERV to either human or porcine cells. Such animals were identified within the miniature swine herd and may further enhance the safety of clinical xenotransplantation.

scholarly journals Effect of Vitamin D3 On the Expression of Antimicrobial Peptide Gene in Experimental Pneumonia in Calf

2021 ◽  
Author(s):  
Parisa Asgharpour ◽  
Zohre Eftekhari ◽  
Mohammad Goli Nadealian ◽  
Gholam Reza Nikbakht Borojeni ◽  
Mohammad Reza Mokhber Dezfouli
Keyword(s):  
Vitamin D ◽  
Treatment Group ◽  
Vitamin D3 ◽  
Pasteurella Multocida ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Cell Content ◽  
Peripheral Blood Mononuclear

Abstract Background Vitamin D3 has been identified as an immunomodulatory agent that confronts the pathogens via stimulating antimicrobial peptides (AMPs). Objective The effects of vitamin D3 on the expression of AMPs was assessed in experimental pasteurellosis in calves. Methods 10 Holstein crossbred male calves (2–4 months) were chosen and randomly divided into the two groups. Pasteurella multocida was prepared (3×109 CFU/mL) and inoculated in the trachea. Vitamin D3 was injected to the treatment group after confirming the pneumonia. Blood samples were obtained from both groups at different time intervals and the peripheral blood mononuclear cells (PBMCs) were isolated. Clinical symptoms were recorded. Broncho-alveolar lavage was performed to evaluate the lung cell content. On the other hand, 10− 6, 10− 7, and 10 − 8 molar (M) of vitamin D3, was used to evaluate the expression of CD4, BMAP34, and BNBD4 genes using PBMCs under the in vitro conditions. Results The prescription of vitamin D3 to the treatment group caused a decline in clinical signs. Following the vitamin D3 injections the treatment groups under the in vivo conditions, significant increase was observed in the expression level of Defensin (BNBD4), and CD4. Evaluation of bronchoalveolar lavage fluid (BALF) revealed that the amount of neutrophils decreased after vitamin D injection. In vitro, increased expression of Catalicidin (BMAP34), Defensin (BNBD4), and CD4 was observed at a concentration of 10− 6 M of vitamin D3. Conclusion The present study indicated that vitamin D3, exerts immunomodulatory effects on many infectious diseases via activation of VDR pathways and stimulation of AMP production.

scholarly journals Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences

2008 ◽  
Vol 82 (17) ◽  
pp. 8743-8761 ◽  
Author(s):  
Andrew E. Armitage ◽  
Aris Katzourakis ◽  
Tulio de Oliveira ◽  
John J. Welch ◽  
Robert Belshaw ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human polynucleotide cytidine deaminases APOBEC3G (hA3G) and APOBEC3F (hA3F) are antiviral restriction factors capable of inducing extensive plus-strand guanine-to-adenine (G-to-A) hypermutation in a variety of retroviruses and retroelements, including human immunodeficiency virus type 1 (HIV-1). They differ in target specificity, favoring plus-strand 5′GG and 5′GA dinucleotide motifs, respectively. To characterize their mutational preferences in detail, we analyzed single-copy, near-full-length HIV-1 proviruses which had been hypermutated in vitro by hA3G or hA3F. hA3-induced G-to-A mutation rates were significantly influenced by the wider sequence context of the target G. Moreover, hA3G, and to a lesser extent hA3F, displayed clear tetranucleotide preference hierarchies, irrespective of the genomic region examined and overall hypermutation rate. We similarly analyzed patient-derived hypermutated HIV-1 genomes using a new method for estimating reference sequences. The majority of these, regardless of subtype, carried signatures of hypermutation that strongly correlated with those induced in vitro by hA3G. Analysis of genome-wide hA3-induced mutational profiles confirmed that hypermutation levels were reduced downstream of the polypurine tracts. Additionally, while hA3G mutations were found throughout the genome, hA3F often intensely mutated shorter regions, the locations of which varied between proviruses. We extended our analysis to human endogenous retroviruses (HERVs) from the HERV-K(HML2) family, finding two elements that carried clear footprints of hA3G activity. This constitutes the most direct evidence to date for hA3G activity in the context of natural HERV infections, demonstrating the involvement of this restriction factor in defense against retroviral attacks over millions of years of human evolution.

scholarly journals Identification and Characterization of Two Closely Related Unclassifiable Endogenous Retroviruses in Pythons (Python molurus and Python curtus)

2002 ◽  
Vol 76 (15) ◽  
pp. 7607-7615 ◽  
Author(s):  
Jon B. Huder ◽  
Jürg Böni ◽  
Jean-Michel Hatt ◽  
Guido Soldati ◽  
Hans Lutz ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Peripheral Blood Mononuclear ◽  
Python Regius ◽  
Boa Constrictor ◽  
Inclusion Body Disease ◽  
Python Molurus

ABSTRACT Boid inclusion body disease (BIBD) is a fatal disorder of boid snakes that is suspected to be caused by a retrovirus. In order to identify this agent, leukocyte cultures (established from Python molurus specimens with symptoms of BIBD or kept together with such diseased animals) were assessed for reverse transcriptase (RT) activity. Virus from cultures exhibiting high RT activity was banded on sucrose density gradients, and the RT peak fraction was subjected to highly efficient procedures for the identification of unknown particle-associated retroviral RNA. A 7-kb full retroviral sequence was identified, cloned, and sequenced. This virus contained intact open reading frames (ORFs) for gag, pro, pol, and env, as well as another ORF of unknown function within pol. Phylogenetic analysis showed that the virus is distantly related to viruses from both the B and D types and the mammalian C type but cannot be classified. It is present as a highly expressed endogenous retrovirus in all P. molurus individuals; a closely related, but much less expressed virus was found in all tested Python curtus individuals. All other boid snakes tested, including Python regius, Python reticulatus, Boa constrictor, Eunectes notaeus, and Morelia spilota, were virus negative, independent of whether they had BIBD or not. Virus isolated from P. molurus could not be transmitted to the peripheral blood mononuclear cells of B. constrictor or P. regius. Thus, there is no indication that this novel virus, which we propose to name python endogenous retrovirus (PyERV), is causally linked with BIBD.

scholarly journals 183 Small nucleolar RNA SNORD3A: a potential new biomarker and molecular player in heart failure

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Roberta Paolillo ◽  
Giacomo Gabriele Schiattarella ◽  
Stefania D'Apice ◽  
Christopher Holley ◽  
Alessandro Della Corte ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Survival ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Sequencing Analysis ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Blood Mononuclear Cells

Abstract Aims Despite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of myocardial human tissues, identification of circulating biomarkers mirroring myocardial pathological signalling pathways, especially in peripheral blood mononuclear cells (PBMC) is expected to be extremely relevant. Small Nucleolar RNAs (snoRNAs) have been shown to play important roles in various cellular physiological processes. However, the connection between snoRNAs and pathological dysfunction in the heart or peripheral blood mononuclear cells (PBMC) is still poorly understood. To identify novel circulating PBMC biomarkers linked to myocardial dysfunction and HF. Methods Myocardial left ventricle (LV) samples and PBMC were obtained from patients affected by ischaemic HF (HF, n = 13) undergoing heart transplantation and control donors (CD, n = 7) and analysed by RNA sequencing analysis (RNASeq). SNORD3A expression levels in the different groups were evaluated by quantitative real-time PCR. HF was induced in 8-week-old wild type C57BL/6 mice by transverse aortic constriction (TAC). Sham-operated mice (sham) were used as controls. After 12-week-TAC (12w) or sham operation, mice were anesthetized, cardiac function was analysed by echocardiography, and cardiac/PBMC samples were collected after sacrifice. In order to test the role of SNORD3A in cardiomyocyte hypoxia, H9C2 cardiomyoblasts were transfected with SNORD3A-targeted antisense oligonucleotides (ASO) and cell survival was analysed. Results RNASeq analysis identified a small set of genes differentially expressed in the heart and PBMC from HF patients. Among these, SNORD3A was up-regulated in cardiac and PBMC samples from HF patients compared to CD (Figure 1A). Similarly, in murine HF induced by 12w TAC, SNORD3A levels were increased by rtPCR, both in the heart and PBMC (Figure 1B). SNORD3A expression levels were also significantly increased in H9C2 cells exposed to in vitro hypoxia (Figure 1C). Interestingly, H9C2 transfection with SNORD3A-specific ASO significantly reduced hypoxia-induced SNORD3A up-regulation and reduced hypoxia-induced cell death (Figure 1D). Conclusions In this study, we identify SNORD3A as a novel possible biomarker in human HF, similarly up-regulated in the heart and PBMC, induced by hypoxia in vitro and modulating cell survival.

scholarly journals Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models

2001 ◽  
Vol 82 (4) ◽  
pp. 837-844 ◽  
Author(s):  
Volker Specke ◽  
Stefan J. Tacke ◽  
Klaus Boller ◽  
Jochen Schwendemann ◽  
Joachim Denner
Keyword(s):  
Cell Lines ◽  
Mononuclear Cells ◽  
Small Animal ◽  
Endogenous Retroviruses ◽  
Productive Infection ◽  
Transgenic Pigs ◽  
Peripheral Blood Mononuclear ◽  
Porcine Endogenous Retrovirus ◽  
Wide Range

Using transgenic pigs as the source of cells or organs for xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Multiple proviruses are integrated into the genome of all pigs, and virus particles, some of which are able to infect human cells, are released from normal pig cells. In order to evaluate the potential risk posed by the transmission of PERVs, in vitro infection studies were performed as a basis for small animal as well as non-human primate models. In vitro infectivity was demonstrated for permanent cell lines and primary cells from a wide range of species. Productive infection was shown using reverse transcriptase (RT) assays and RT–PCR for mink, feline and human kidney cell lines, primary rhesus peripheral blood mononuclear cells (PBMCs), and baboon spleen cells and PBMCs as well as for different human lymphoid and monocyte cell lines and PBMCs. In an attempt to establish a small animal model, naive guinea pigs, non-immunosuppressed rats, rats immunosuppressed by cyclosporin-A and immunosuppressed rats treated with cobra venom factor were inoculated with PERVs produced from porcine kidney PK-15 cells, infected human 293 kidney cells and mitogen-stimulated porcine PBMCs. Animals were also inoculated with PERV-producing PK-15 and 293 cells. No antibodies against PERV and no provirus integration were observed in any of the treated animals. This suggests that productive infection of these animals did not occur in this experimental setting.

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