Human Endogenous Retrovirus type W characterization in genome assembly GRCh37/hg19: an innovative approach for human diseases investigation

GRANDI, NICOLE;CADEDDU, MARTA;Vargiu L;Rodriguez Tomé P;Blomberg J;Tramontano E.

2014-01-01

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Abstract

About 8% of our genome is composed by Endogenous Retrovirus sequences (HERVs), integrated in germ line cells and vertically transmitted through the offspring. The HERVW group belongs to class I Gammaretroviruses and one provirus, locus ERVWE1, has a full length sequence producing a functional env protein, Syncytin-1, coopted during evolution for the pregnancy syncytiotrophoblast formation. In addition, HERVW transcripts have been found in several pathogenic tissues, hypothesizing an involvement in various neurologic disorders and different tumors. Despite the emerging scenery proposes HERVW elements as determinant contributors in human diseases, insufficient information on group composition and genomic distribution are currently available. The GRCh37/hg19 assembly was analyzed with RetroTector software and 126 sequences containing HERVW portions, the great majority not previously described, were identified and exactly localized. Proviruses were classified in canonical and non canonical according to their similarity with reference sequences, and the presence of both LTRs permitted age estimation for ∼20% of them. The viral ORFs were identified, and a phylogenetic investigation of the putative proteins were performed. A detailed structural analysis allowed viral subgenes characterization and highlighted the presence of mutations and typical features. The proviral structure and the integration context are known to influence viral expression. HERVW characterization, hence, is an essential step to clarify their contribution to diseases with poorly understood etiology, and provides the basis to elect them as both potential powerful markers and innovative therapeutic targets.