Unbiased examination of genome-wide human endogenous retrovirus transcripts in MS brain lesions

2021 ◽  
pp. 135245852098726
Author(s):  
Maria L Elkjaer ◽  
Tobias Frisch ◽  
Arianna Tonazzolli ◽  
Richard Röttger ◽  
Richard Reynolds ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Potential Role ◽  
Brain Lesion ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus ◽  
High Quality ◽  
Genome Wide ◽  
And Control ◽  
Herv Expression

Background: Human endogenous retrovirus (HERV) expression in multiple sclerosis (MS) brain lesions may contribute to chronic inflammation, but expression of genome-wide HERVs in different MS lesions is unknown. Objective: We examined the HERV expression landscape in different MS lesions compared to control brains. Methods: Transcripts from 71 MS brain samples and 25 control WM were obtained by next-generation RNA sequencing and mapped against HERV transcripts across the human genome. Differential expression of mapped HERV-W and HERV-H reads between MS lesion types and controls was analysed. Results: Out of 6.38 billion high-quality paired end reads, 174 million reads (2.73%) mapped to HERV transcripts. There was no difference in HERVs expression level between MS and control brains, but HERV-W transcripts were significantly reduced in chronic active lesions. Of the four HERV-W transcripts exclusively present in MS, ERV3633503 located on chromosome 7q21.13 close to the MS genetic risk locus had the highest number of reads. In the HERV-H family, 75% of transcripts located to nearby 7q21-22 were overrepresented in MS, and ERV3643914 was expressed more than 16 times in MS compared to control brains. Conclusion: Novel HERV-W and HERV-H transcripts located at chromosome 7 regions were uniquely expressed in MS lesions, indicating their potential role in brain lesion evolution.

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 Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis

2016 ◽  
Vol 8 ◽  
pp. 11-18 ◽  
Author(s):  
Jack van Horssen ◽  
Susanne van der Pol ◽  
Philip Nijland ◽  
Sandra Amor ◽  
Hervé Perron
Keyword(s):  
Multiple Sclerosis ◽  
Targeted Therapy ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus

scholarly journals Comprehensive Analysis of HERV Transcriptome in HIV+ Cells: Absence of HML2 Activation and General Downregulation of Individual HERV Loci

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 481 ◽  
Author(s):  
Nicole Grandi ◽  
Maria Paola Pisano ◽  
Sante Scognamiglio ◽  
Eleonora Pessiu ◽  
Enzo Tramontano
Keyword(s):  
Hiv Infection ◽  
De Novo ◽  
Endogenous Retrovirus ◽  
Open Reading Frames ◽  
Human Endogenous Retrovirus ◽  
Bioinformatics Pipeline ◽  
Transcriptional Modulation ◽  
Herv Expression ◽  
Coding Potential ◽  
Hiv 1

Human endogenous retrovirus (HERV) expression is currently studied for its possible activation by HIV infection. In this context, the HERV-K(HML2) group is the most investigated: it has been proposed that HIV-1 infection can prompt HML2 transcription, and that HML2 proteins can affect HIV-1 replication, either complementing HIV or possibly influencing antiretroviral therapy. However, little information is available on the expression of other HERV groups in HIV infection. In the present study, we used a bioinformatics pipeline to investigate the transcriptional modulation of approximately 3250 well-characterized HERV loci, comparing their expression in a public RNA-seq profile, including a HIV-1-infected and a control T cell culture. In our pilot study, we found approximately 200 HERV loci belonging to 35 HERV groups that were expressed in one or both conditions, with transcripts per million (TPM) values from 1 to >500. Intriguingly, HML2 elements constituted only the 3% of expressed HERV loci, and in most cases (160) HERV expression was downregulated in the HIV-infected culture, showing from a 1- to 14-fold decrease as compared to uninfected cells. HERV transcriptome has been inferred de novo and employed to predict a total of about 950 HERV open reading frames (ORFs). These have been validated according to the coding potential and estimated abundance of the corresponding transcripts, leading to a set of 57 putative proteins potentially encoded by 23 HERV loci. Analysis showed that some individual loci have a coding potential that deserves further investigation. Among them, a HML6 provirus at locus 19q13.43 was predicted to produce a transcript showing the highest TPM among HERV-derived transcripts, being upregulated in HIV+ cells and inferred to produce Gag and Env puteins with possible biological activity.

scholarly journals Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics

2021 ◽  
Author(s):  
Benjamin Charvet ◽  
Justine Pierquin ◽  
Joanna Brunel ◽  
Rianne Gorter ◽  
Christophe Quétard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus ◽  
Soluble Antigen ◽  
Physico Chemical ◽  
Demyelinating Lesions ◽  
Ms Pathogenesis

AbstractIn multiple sclerosis (MS), human endogenous retrovirus W family (HERV-W) envelope protein, pHERV-W ENV, limits remyelination and induces microglia-mediated neurodegeneration. To better understand its role, we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies. Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1. pHERV-W ENV monomers and trimers remained associated with membranes, while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain. Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties. HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described high-molecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis. Adapted methods are now needed to identify encoding HERV provirus(es) in affected cells DNA. The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis. The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.

RANTES: a genetic risk marker for multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 536-539 ◽  
Author(s):  
Radhika Gade-Andavolu ◽  
David E Comings ◽  
James MacMurray ◽  
Ravi K Vuthoori ◽  
Wallace W Tourtellotte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Promoter Region ◽  
Potential Role ◽  
Primary Diagnosis ◽  
Brain Lesions ◽  
Postmortem Brain ◽  
Proximal Promoter ◽  
Promoter Polymorphisms ◽  
Functional Polymorphisms

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls. Methods: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects. The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects were non-Hispanic Caucasians. Results: MS cases differed from controls showing a significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465-3.799]; P-0.0001), but not the -28C/G (P-NS) polymorphism. There was a significant association of the -28G allele with both early onset (P-0.031) and longer survival (P-0.006). Conclusion: There is a significant but complex association of the RANTES gene with MS.

Sign in / Sign up

Export Citation Format

Share Document