Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens; Mayer, Jens

doi:10.1128/jvi.02388-13

Cited by 63 publications

(73 citation statements)

References 61 publications

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“…The widespread and tissue‐specific expression of HERV‐W can consequently be attributed to both LTR‐directed transcription and transcriptional leakage . A recent study using a luciferase reporter assay reported promoter activity of HERV‐W with incomplete LTRs thereby confirming our previous observations . Our current observations from ongoing analyses of RNA sequencing data are also consistent with this finding, where we detect expression from partially fragmented LTRs of pseudoelements.…”

Section: Transcriptional Regulation Of Herv‐wsupporting

confidence: 90%

Expression and regulation of human endogenous retrovirus W elements

Karlsson

2016

APMIS

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Human endogenous retroviruses (HERV) comprise 8% of the human genome and can be classified into at least 31 families. A typical HERV provirus consists of internal gag, pol and env genes, flanked by two long terminal repeats (LTRs). No single provirus is capable of engendering infectious particles. HERV are by nature repetitive and have with few notable exceptions lost their protein-coding capacity. Therefore, HERV have consistently been excluded from array-based expression studies and hence little is known of their expression, regulation, and potential functional significance. An increasing number of studies have, however, observed expression of the W family of HERV in various human tissues and cells, predominantly in placenta. HERV-W LTRs act as promoters in directing transcription of HERV-W members, contribute to their tissue-specific and highly diversified expression pattern. Furthermore, leaky transcription originating from adjacent genes plays a role in the transcription initiation of HERV-W psudoelements. It has been reported that HERV-W elements, including ERVWE1 (the so far only known HERV-W locus harboring a gene (env) functionally adopted by the human host to critically participate in placenta biogenesis), can become transactivated in a range of human non-placental cell-lines during exogenous virus infections. Aberrant expression of HERV-W has been associated with human diseases, such as cancer, multiple sclerosis, and schizophrenia. Based on published reports, transcriptional activities of HERV-W appear to be influenced by several mechanisms; binding of transcription factors to LTR promoters and enhancers outside of LTRs, genetic variation and alteration in DNA methylation and histone modification. Emerging mechanistic studies support the notion that HERV-W represents a potential marker or mediator of environmental exposures (e.g., virus infection) in the development of chronic complex diseases.Key words: HERV-W; LTR-directed; virus infection; aberrant expression; DNA methylation; histone modification.Fang Li, Department of Basic Medical Science, Changsha Medical University, 410219, Changsha, China. e-mail: li-evans@hotmail.com Sequencing of the human genome has revealed that approximately 2% of the genome is composed of protein-coding regions, whereas approximately 8% of our DNA is recognized as containing human endogenous retrovirus (HERV) elements (1, 2). A high prevalence of ERVs in 65 investigated vertebrate genomes, and the detection of highly related sequences in the genomes of distantly related vertebrates was recently reported (3). Thus, infection, endogenization, and intragenomic expansion of a wide range of retroviruses appear to have been common during evolution. Although some individual integration events have clearly been beneficial to the host during evolution, the roles of other integrations and their massive expansions in the host genome remain unclear. Interestingly, differential expression of HERV have been associated with a range of human diseases, such as cancer and multiples ...

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Section: Transcriptional Regulation Of Herv‐wsupporting

confidence: 90%

Expression and regulation of human endogenous retrovirus W elements

Karlsson

2016

APMIS

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“…In particular, 55 HERV-Ws were found into coding genes, 8 more than what previously observed [20, 70], while 25 elements were inserted in human non-coding genes, of which the great majority (22) are reported here for the first time.…”

Section: Discussionsupporting

confidence: 47%

Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes

et al. 2016

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BackgroundHuman endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies.ResultsIn the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported.ConclusionsThe present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0301-x) contains supplementary material, which is available to authorized users.

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“…HERVs have been investigated in a large number of autoimmune disorders due to their role in innate and adaptive immunity based on molecular mimicry . Multiple sclerosis‐associated retrovirus (MSRV) might have originated from the recombination of different HERV‐W transcripts, which was associated with poor prognosis in patients with multiple sclerosis and a higher rate of clinical re‐exacerbations . Syncytin‐1, a HERV‐W env protein, has been found to regulate neuroinflammation in multiple sclerosis .…”

Section: Introductionmentioning

confidence: 99%

Expressional activation and functional roles of human endogenous retroviruses in cancers

Zhang

Liang

Zheng

2019

Reviews in Medical Virology

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Summary Human endogenous retroviruses (HERVs) are widely believed to be remnants of ancestral germ line infections by exogenous retroviruses. Although HERVs are deemed as “nonfunctional DNAs” due to loss of most of their viral protein coding capacity during evolution as part of the human genome, cumulative evidences are showing the expressional activation and potential roles of HERVs in diseases especially cancers. Work by other researchers and us has observed the dysregulation of HERVs in cancers, identified new HERV‐related genes, and revealed their potential importance in cancer development. Here, we summarized the current knowledge on the mechanisms of the expressional activation and functional roles of HERVs, with a focus on the H family HERV (HERV‐H), in carcinogenesis. HERV expression is regulated by external chemical or physical substances and exogenous virus infection, as well as host factors such as epigenetic DNA methylation, transcription factors, cytokines, and small RNAs. Diverse roles of HERVs have been proposed by acting in the forms of noncoding RNAs, proteins, and transcriptional regulators during carcinogenesis. However, much remains to be learnt about the contributions of HERVs to human cancers. More investigation is warranted to elucidate the functions of these “fossil remnants” yet important viral DNAs in the human genome.

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Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

Cited by 63 publications

References 61 publications

Expression and regulation of human endogenous retrovirus W elements

Expression and regulation of human endogenous retrovirus W elements

Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes

Expressional activation and functional roles of human endogenous retroviruses in cancers

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