Human endogenous retrovirus K (HERV-K) is expressed in villous and extravillous cytotrophoblast cells of the human placenta

Kämmerer, Ulrike; Germeyer, Ariane; Stengel, Sven; Kapp, Michaela; Denner, Joachim

doi:10.1016/j.jri.2011.06.102

Cited by 57 publications

(84 citation statements)

References 42 publications

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“…Sperm express syncytin-1 on the cell surface whereas oocytes do not; instead, oocytes express the syncytin-1 receptor SLC1A5 [65]. Finally, HERV-K particles have also been detected in human placenta [72] but the functional significance of this, if any, remains unclear.…”

Section: Examples Of Herv Regulationmentioning

confidence: 99%

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

Hurst

Magiorkinis

2017

Viruses

105

100

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Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology.

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Section: Examples Of Herv Regulationmentioning

confidence: 99%

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

Hurst

Magiorkinis

2017

Viruses

105

100

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“…Given this hypomethylation of LTRs in placentas, it is not surprising that numerous sub-families of ERV proviruses are expressed within human placental tissues. More specifically, there is evidence of proviral transcription from ERV-E (Yi and Kim, 2007), ERV3 (ERV-R; Boyd et al, 1993; Andersson et al, 2005), ERV-K (Kammerer et al, 2011), ERV-fb1 (Sugimoto et al, 2013), ERV-V1/2 (Esnault et al, 2013), ERV-W (Blond et al, 2000), and ERV-FRD (Blaise et al, 2003; Supplementary Tables 1, 2). …”

Section: Ervs In the Placentamentioning

confidence: 99%

“…This is based on findings that both families have one or more proviral loci in the genome with intact env open reading frames (ORFs) and a corresponding immunosuppressive domain. Additionally, both ERV-V and ERV-K expression has been observed within placental trophoblast cells at the maternal-fetal interface, although corresponding in vitro functional assays have not yet been completed to directly support in vivo findings (Kammerer et al, 2011; Subramanian et al, 2011; Supplementary Table 1). Until these studies are undertaken, the exact function of ERV-V and ERV-K and whether env protein expression from these ERVs induce maternal immunosuppression within the placenta, will remain unknown.…”

Section: Ervs In the Placentamentioning

confidence: 99%

Endogenous Retroviruses: With Us and against Us

et al. 2017

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Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe how disruption of the regulated mechanisms of ERVs may impact somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

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“…Androgensignaling brings these two genes into proximity, thus inducing their fusion (313). Altogether, the untranslated 5'UTR region of gene TMPRSS2 (21q22) may fuse with ERG (21q22), ETV1 (7p21), SLC45A3 9 (solute carrier gene) and with HERVK, the human endogenous retrovirus gene, that in extravillous cytotrophoblasts exerts immunosuppressive properties in the defense of the fetus (314,315) (318).…”

Section: Ebvmentioning

confidence: 99%

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

Sinkovics

2011

Int J Oncol

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Abstract. In some inflammasomes tumor cells are generated. The internal environment of the inflammasome is conducive to the induction of malignant transformation. Epigenetic changes initiate this process. The subverted stromal connective tissue cells act to promote and sustain the process of malignant trans formation. In its early stages, the premalignant cells depend on paracrine circuitries for the reception of growth factors. The ligands are derived from the connective tissue, and the receptors are expressed on the recipient premalignant cells. The initial events are not a direct attack on the protooncogenes, and thus it may be entirely reversible. Epigenetic processes of hypermethylation of the genes at the promoters of tumor suppressor genes (to silence them), and deacetylation of the histones aimed at the promoters of protooncogenes (to activate them) are ongoing. A large number of short RNA sequences (interfering, micro, short hairpin, noncoding RNAs) silence tumor suppressor genes, by neutralizing their mRNAs. In a serial sequence oncogenes undergo amplifications, pointmutations, translocations and fusions. In its earliest stage, the process is reversible by demethylation of the silenced suppressor gene promoters (to reactivate them), or reacetylation of the histones of the oncogene promoters, thus deactivating them. The external administration of histone deacetylase inhibitors usually leads to the restoration of histone acetylation. In time, the uncorrected processes solidify into constitutive and irreversible gene mutations. Some of the pathogens inducing inflammations with consquential malignant transformation contain oncogenic gene sequences (papilloma viruses, EpsteinBarr virus, Kaposi's sarcomaassociated herpesvirus, hepatitis B and C viruses, Merkel cell polyoma virus, Helicobacter pylori, enterotoxigenic Bacteroides fragilis). These induced malignancies may be multifocal. Other pathogens are devoid of any known oncogenic genomic sequences (mycoplasma vavcarcinogenesis, chlamydia MALTlymphoma genesis). In these cases the host's inflammatory reactions induce the malignant transformation in serial sequences of gene alterations initiated by hypoxia and reactive oxygen and nitrogen species generation. Carcinogenic intrinsic inflammatory processes endogenously initiated without a pathogen are recognized. Chronic inflammatory processes signal the RNA/DNA complex. In response, the DNA may revert into its ancient primordial 'immortal' format, which the clinics recognize as 'oncogenesis'. The DNA remains the ultimate master of bioengineering in order to sustain life. A discussion on the most versatile and resistant primordial RNA/ DNA complex and the pre, proto, and unicellular world in which they coexisted is included. Contents1. Pathogens without oncogenic genomic sequences activating cellular oncogenes 2. The inflammasome 3. Tumor cell colonies generated in the inflammasomes 4. Pathogens with potentially oncogenic genomic sequences 5. Mechanisms of inflammatory carcinogenesis Pathogens without oncogenic...

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Human endogenous retrovirus K (HERV-K) is expressed in villous and extravillous cytotrophoblast cells of the human placenta

Cited by 57 publications

References 42 publications

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

Endogenous Retroviruses: With Us and against Us

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

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