WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous Retrovirus-Like Sequences

Abstract

More than eight percent of the human genome consists of human endogenous retroviruses (HERVs). Typically, the expression of HERVs is repressed, but varying activities of HERVs have been observed in diseases ranging from cancer to neuro-degeneration. Such activities can include the transcription of HERV-derived open reading frames, which can be translated into proteins. However, as a consequence of mutations that disrupt open reading frames, most HERV-like sequences have lost their protein-coding capacity. Nevertheless, these loci can still influence the expression of adjacent genes and, hence, mediate biological effects. Here, we present WebHERV (http://calypso.informatik.uni-halle.de/WebHERV/), a web server that enables the computational prediction of active HERV-like sequences in the human genome based on a comparison of genome coordinates of expressed sequences uploaded by the user and genome coordinates of HERV-like sequences stored in the specialized key-value store DRUMS. Using WebHERV, we predicted putative candidates of active HERV-like sequences in Hodgkin lymphoma (HL) cell lines, validated one of them by a modified SMART (switching mechanism at 5′ end of RNA template) technique, and identified a new alternative transcription start site for cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1).

Expression of A New Endogenous Retrovirus-Associated Transcript in Hodgkin Lymphoma Cells

“…Endogenous retrovirus (ERV)-like elements (ERVLE) have been shown to be activated in HL cells [15,16,17,18]. For instance, expression of the colony stimulating factor 1 (CSF1) receptor (CSF1R) in HL cells is driven by a long terminal repeat (LTR) from an ERVLE [15].…”