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Review
. 2015 Mar 16;7(3):1238-57.
doi: 10.3390/v7031238.

Human endogenous retrovirus group E and its involvement in diseases

Christelle Le Dantec  1 , Sophie Vallet  2 , Wesley H Brooks  3 , Yves Renaudineau  1   4
Affiliations
Review

Human endogenous retrovirus group E and its involvement in diseases

Christelle Le Dantec et al. Viruses. .

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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Figures

Figure 1
Figure 1
The phylogenetic tree of the 5’ LTR HERV-E sequences reveals three main subgroups: LTR2, LTR2B and LTR2C. Phylogenetic analyses were inferred using the Maximum Parsimony Methods on the ClustalW Multiple alignment of 46 HERV-E 5’LTR nucleotide sequences. The most parsimonious tree is shown; it shows that the 46 HERV-E LTRs are segregated into 3 distinct subgroups. Bootstrap values greater than 50% are shown. The 5’ HERV-E LTR sequences are identified with their respective human chromosomal locus location (See Experimental Section plus Table 1). When known, the gene used for alternative transcript usage is reported.
Figure 2
Figure 2
Putative integration times of the LTR2, LTR2B, LTR2C HERV-E familly members during primate evolution. The evolutionary tree was adapted from Yi et al. [12,13].
Figure 3
Figure 3
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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