Transcriptional landscape of human endogenous retroviruses (HERVs) and other repetitive elements in psoriatic skin

Freddy Lättekivi,Maris Keermann,Ele Prans,Sulev Kõks,Helgi Silm,Kristi Abram,Gea Kõks,Ene Reimann,Külli Kingo

doi:10.1038/s41598-018-22734-7

Abstract

Human endogenous retrovirus (HERV) sequences make up at least 8% of the human genome. Transcripts originating from these loci as well as proteins encoded by them have been detected in various tissues. HERVs are believed to be implicated in autoimmune diseases, however the extent to which, has remained unclear. Differential expression studies have so far been limited to certain HERV subfamilies with conserved sequences. No studies have been published describing the genome-wide expression pattern of HERVs and repetitive elements in the context of psoriasis. In the present study, we analysed total RNA sequencing data from skin samples of 12 psoriasis patients and 12 healthy controls, which enabled us to describe the entire transcriptional landscape of repetitive elements. We report high levels of repetitive element expression in the skin of psoriasis patients as well as healthy controls. The majority of differentially expressed elements were downregulated in lesional and non-lesional skin, suggesting active HERV suppression in the pro-inflammatory environment of psoriatic skin. However, we also report upregulation of a small subset of HERVs previously described in the context of autoimmune diseases, such as members of the HERV-K and W families, with the potential to affect the immunopathogenesis of psoriasis.

Highlights

Human endogenous retroviruses (HERVs), members of the long terminal repeat (LTR) retrotransposons repetitive element class, make up at least 8–10% of the human genome[1]
Transcripts originating from a copy of HERV-K deoxyuridine triphosphate nucleotidohydrolase, located within the psoriasis susceptibility 1 (PSORS1) locus, have been found in both peripheral blood mononuclear cells (PBMCs) and skin tissue[13]
With on average 27.5% of reads aligning to repetitive element loci, the expression of repetitive elements was prominent in all the 12 lesional skin (LP), 12 non-lesional skin (NLP) and 12 healthy control (C) samples investigated

Summary

Introduction

Human endogenous retroviruses (HERVs), members of the long terminal repeat (LTR) retrotransposons repetitive element class, make up at least 8–10% of the human genome[1]. Expression of retroviral polymerase (pol) encoding members of the HERV-W, K and E families have been reported in psoriatic skin, while rarely detected in non-lesional skin[12]. Element Class SINE Satellite scRNA LTR srpRNA DNA snRNA RNA LINE RC or pol sequences in the lesional skin of psoriasis patients compared to non-lesional skin and healthy skin from control group subjects[15]. We re-analysed our previously published RNA-seq data[16,17], utilizing the RepEnrich pipeline[18] in order to investigate the genome-wide transcriptional landscape of HERVs and repetitive elements in the lesional and non-lesional skin of psoriasis patients

Methods

Results

Conclusion