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Titolo: Human Endogenous Retrovirus type W distribution in the human genome: identification and characterization of a new set of proviral sequences in GRCh37/hg19 assembly
Data di pubblicazione: 2014
Abstract: About 8% of the human genome is composed by Endogenous Retrovirus sequences (HERVs) that after an ancestral infection have been integrated in the germ line cells and vertically transmitted through the offspring. The HERVW group belongs to class I Gammaretroviruses and one provirus, named locus ERVWE1, has a full length sequence producing a functional env protein, Syncytin-1, that during evolution has been coopted for the pregnancy syncytiotrophoblast formation. In addition, some HERVWs have been investigated for their putative role in various neurologic diseases, such as Multiple Sclerosis and Schizofrenia. However, despite some studies on HERVW expression, insufficient information on the viral group composition and genomic distribution are currently available. The characterization of HERVW sequences, hence, is an essential step for better understanding their persistence and their potential role in both physiological and pathological contexts. The GRCh37/hg19 genome assembly was analyzed with RetroTector software and 126 sequences containing HERVW portions were identified, the great majority not previously characterized. Based on their similarity with the reference sequences they were classified in canonical (62) and non canonical (64). HERVW proviruses are present in all chromosomes except 16 and 22. The presence of both LTRs allowed age estimation for ∼20% of the sequences. Phylogenetic investigation and detailed structural analysis showed an high conservation of gag, pro and the first portion of pol, while the pol C-terminal part and the entire env gene was the most variable or absent. The Gammaretroviral structural features research supported the structural analysis: only 10% proviruses maintained the C-terminal of pol IN GPY/F domain, whereas about 80% of sequences showed a highly conserved Gag Zinc-finger motif. Moreover, a second highly conserved Zinc-finger was detected in 56% HERVW sequences, previously reported only in HERVH Gammaretroviruses. The emerging scenery proposes HERVW elements as determinant contributors in human diseases. This emphasizes the pressing need of their detailed characterization in the genomic context, providing the basis to clarify the role of HERVW proviruses in the pathogenesis of diseases with poorly understood etiology.
Tipologia:4.2 Abstract in Atti di convegno

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