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Human endogenous retrovirus group E and its involvement in diseases.

Le Dantec C, Vallet S, Brooks WH, Renaudineau Y - Viruses (2015)

Bottom Line: Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C.Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production.Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy.

View Article: PubMed Central - PubMed

Affiliation: INSERM ESPRI, ERI29/EA2216, SFR ScInBioS, LabEx IGO "Immunotherapy Graft Oncology", Réseau épigénétique et réseau canaux ioniques du Cancéropole Grand Ouest, European University of Brittany, Brest 29609, France. yves.renaudineau@univ-brest.fr.

ABSTRACT
Human endogenous retrovirus group E (HERV-E) elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy.

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Related in: MedlinePlus

Examples of five integrated HERV-Es in the vicinity of PTN, MID1, CD5, FABP7 and ZNF66 human genes. HERV-E is depicted as a black rectangle (5’LTR) linked to a white rectangle (3’LTR). The direction of gene transcription is indicated (black arrow). Black boxes refer to exons, and fusion transcripts are indicated.
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viruses-07-01238-f003: Examples of five integrated HERV-Es in the vicinity of PTN, MID1, CD5, FABP7 and ZNF66 human genes. HERV-E is depicted as a black rectangle (5’LTR) linked to a white rectangle (3’LTR). The direction of gene transcription is indicated (black arrow). Black boxes refer to exons, and fusion transcripts are indicated.

Mentions: Analysis of the human Expressed Sequence Tag (EST) database reveals an important proportion of HERVs and LTR elements in the transcriptome and, among them, HERV-Es are overrepresented and initiate 9.3% of the chimeric LTR transcripts when leukemic B cells from diffuse large B cell lymphoma are analyzed [18]. In general, when the HERV element is in the sense strand, upstream of the host promoter (exon 1) or in the first intron, the HERV element can act as an alternative promoter, splice with exon 2, and generate a fusion mRNA with a longer 5’ untranslated region (UTR). The splicing of the HERV element to a splice acceptor site in the host gene sequence could shift the open reading frame (ORF), yielding a transcript that cannot be translated into the functional host gene product as observed with HERV-E.CD5 (Figure 3). In contrast, when HERV elements are in the anti-sense strand relative to neighbouring host genes, the active HERV element could either disrupt expression of the host genes, dampening the host gene activity or act as a promoter (e.g., HERV-E.FABP7) or an enhancer (e.g., HERV-E.AMY1B [19,20]) to promote an alternative tissue expression. When the HERV element is in the body of a host gene, the HERV can provide additional splice donor site(s), acceptor site(s), or premature polyadenylation signals resulting in creation of incorrectly spliced and/or truncated variants.


Human endogenous retrovirus group E and its involvement in diseases.

Le Dantec C, Vallet S, Brooks WH, Renaudineau Y - Viruses (2015)

Examples of five integrated HERV-Es in the vicinity of PTN, MID1, CD5, FABP7 and ZNF66 human genes. HERV-E is depicted as a black rectangle (5’LTR) linked to a white rectangle (3’LTR). The direction of gene transcription is indicated (black arrow). Black boxes refer to exons, and fusion transcripts are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379568&req=5

viruses-07-01238-f003: Examples of five integrated HERV-Es in the vicinity of PTN, MID1, CD5, FABP7 and ZNF66 human genes. HERV-E is depicted as a black rectangle (5’LTR) linked to a white rectangle (3’LTR). The direction of gene transcription is indicated (black arrow). Black boxes refer to exons, and fusion transcripts are indicated.
Mentions: Analysis of the human Expressed Sequence Tag (EST) database reveals an important proportion of HERVs and LTR elements in the transcriptome and, among them, HERV-Es are overrepresented and initiate 9.3% of the chimeric LTR transcripts when leukemic B cells from diffuse large B cell lymphoma are analyzed [18]. In general, when the HERV element is in the sense strand, upstream of the host promoter (exon 1) or in the first intron, the HERV element can act as an alternative promoter, splice with exon 2, and generate a fusion mRNA with a longer 5’ untranslated region (UTR). The splicing of the HERV element to a splice acceptor site in the host gene sequence could shift the open reading frame (ORF), yielding a transcript that cannot be translated into the functional host gene product as observed with HERV-E.CD5 (Figure 3). In contrast, when HERV elements are in the anti-sense strand relative to neighbouring host genes, the active HERV element could either disrupt expression of the host genes, dampening the host gene activity or act as a promoter (e.g., HERV-E.FABP7) or an enhancer (e.g., HERV-E.AMY1B [19,20]) to promote an alternative tissue expression. When the HERV element is in the body of a host gene, the HERV can provide additional splice donor site(s), acceptor site(s), or premature polyadenylation signals resulting in creation of incorrectly spliced and/or truncated variants.

Bottom Line: Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C.Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production.Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy.

View Article: PubMed Central - PubMed

Affiliation: INSERM ESPRI, ERI29/EA2216, SFR ScInBioS, LabEx IGO "Immunotherapy Graft Oncology", Réseau épigénétique et réseau canaux ioniques du Cancéropole Grand Ouest, European University of Brittany, Brest 29609, France. yves.renaudineau@univ-brest.fr.

ABSTRACT
Human endogenous retrovirus group E (HERV-E) elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy.

Show MeSH
Related in: MedlinePlus