Endogenous retroviruses: acquisition, amplification and taming of genome invaders

Dewannieux, Marie; Heidmann, Thiérry

doi:10.1016/j.coviro.2013.08.005

Cited by 115 publications

(97 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This element successfully amplified via an extracellular pathway involving retroviral particle exit from the cell and reinfection, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. HERVs fixed in the genome and became inheritable because their insertions occurred in the germ cell lineage [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…While most EVE sequences are highly degenerated, it is clear that at least a proportion of these elements have been coopted or "exapted" (i.e., adapted for a function distinct from that for which they originally evolved [10]) to perform physiological functions in their host species (11)(12)(13)(14). Dependovirus-derived EVEs encoding intact replicase proteins have previously been identified in mam- genomes to exogenous parvoviruses and previously described EVEs.…”

mentioning

confidence: 99%

Parvovirus-Derived Endogenous Viral Elements in Two South American Rodent Genomes

Arriagada

Gifford

2014

J Virol

View full text Add to dashboard Cite

bWe describe endogenous viral elements (EVEs) derived from parvoviruses (family Parvoviridae) in the genomes of the longtailed chinchilla (Chinchilla lanigera) and the degu (Octodon degus). The novel EVEs include dependovirus-related elements and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVE was found to carry an intact reading frame and was differentially expressed in vivo, with increased expression in the liver.

show abstract

“…These sequences [called human endogenous retroviruses (HERVs)] share strong similarities with present day retroviruses and are the proviral remnants of ancestral germ-line infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner (1)(2)(3). The >30,000 proviral copies found in the human genome can be grouped into about 80 distinct families, with most of these elements being nonprotein-coding because of the accumulation of mutations, insertions, deletions, and/or truncations (4,5).…”

mentioning

confidence: 99%

HEMO, an ancestral endogenous retroviral envelope protein shed in the blood of pregnant women and expressed in pluripotent stem cells and tumors

Heidmann

Béguin

Paternina

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Capture of retroviral envelope genes is likely to have played a role in the emergence of placental mammals, with evidence for multiple, reiterated, and independent capture events occurring in mammals, and be responsible for the diversity of present day placental structures. Here, we uncover a full-length endogenous retrovirus envelope protein, dubbed HEMO [human endogenous MER34 (mediumreiteration-frequency-family-34) ORF], with unprecedented characteristics, because it is actively shed in the blood circulation in humans via specific cleavage of the precursor envelope protein upstream of the transmembrane domain. At variance with previously identified retroviral envelope genes, its encoding gene is found to be transcribed from a unique CpG-rich promoter not related to a retroviral LTR, with sites of expression including the placenta as well as other tissues and rather unexpectedly, stem cells as well as reprogrammed induced pluripotent stem cells (iPSCs), where the protein can also be detected. We provide evidence that the associated retroviral capture event most probably occurred >100 Mya before the split of Laurasiatheria and Euarchontoglires, with the identified retroviral envelope gene encoding a full-length protein in all simians under purifying selection and with similar shedding capacity. Finally, a comprehensive screen of the expression of the gene discloses high transcript levels in several tumor tissues, such as germ cell, breast, and ovarian tumors, with in the latter case, evidence for a histotype dependence and specific protein expression in clear-cell carcinoma. Altogether, the identified protein could constitute a "stemness marker" of the normal cell and a possible target for immunotherapeutic approaches in tumors.HERV | endogenous retrovirus | envelope protein | placenta | development | stem cells | tumors E ndogenous retroviral sequences represent ∼8% of the human genome. These sequences [called human endogenous retroviruses (HERVs)] share strong similarities with present day retroviruses and are the proviral remnants of ancestral germ-line infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner (1-3). The >30,000 proviral copies found in the human genome can be grouped into about 80 distinct families, with most of these elements being nonprotein-coding because of the accumulation of mutations, insertions, deletions, and/or truncations (4, 5). However, some retroviral genes have retained a coding capacity, and some of them have even been diverted by remote primate ancestors for a physiological role. The so-called "syncytins," namely syncytin-1 and -2 in humans, are retroviral envelope (env) genes captured 25 and 40 Mya, respectively, with a full-length proteincoding sequence, a fusogenic activity, and strong placental expression (6-9). These genes have been shown to be involved in placenta formation, with their fusogenic activity contributing to the formation of the syncytiotrophoblast (ST) at the maternofetal interface as a result of the syncytin-mediated...

show abstract

Endogenous retroviruses: acquisition, amplification and taming of genome invaders

Cited by 115 publications

References 107 publications

Molecular functions of human endogenous retroviruses in health and disease

Molecular functions of human endogenous retroviruses in health and disease

Parvovirus-Derived Endogenous Viral Elements in Two South American Rodent Genomes

HEMO, an ancestral endogenous retroviral envelope protein shed in the blood of pregnant women and expressed in pluripotent stem cells and tumors

Contact Info

Product

Resources

About