Expression profile of Human endogenous retrovirus W (HERV-W)in individuals with Multiples Sclerosis under relapsing conditions

Abstract

The HERVs are endogenous retroviruses , which are set through the host genome integration in the genome of germ cells millions of years ago, now representing about 8% of the human genome. The presence and activity of these in our genome provided the incentive for many studies that attempt to correlate their involvement with autoimmune diseases including multiple sclerosis ( MS) . MS is a autoimmune disease of unknown etiology , treatment is difficult and extremely complex . The disease has an inflammatory stage and is mainly characterized by progressive and degenerative course . Several important findings have raised concern about the possible relationship of HERV family W with MS . Such findings varies from high circulating levels of messenger RNA to the presence of the protein of the env gene of HERV -W on demyelinating lesions of patients with MS. Moreover , it is not known exactly which elements are expressed , and in what proportions . Considering also the highly imunegenic epitope genes of certain retroviruses , it is unclear whether the activity of retrotransposons is able to interfere with the expression of genes related to inflammatory and or immune response to myelin . A tool currently available that can assist in this understanding is the Next Generation Sequencing ( NGS ) . The transcriptome performed by this methodology will provide massive data relating to the entire expression profile of HERV -W , as well as genes responsible for the expression of proinflammatory and anti-inflammatory cytokines in individuals with MS. The main objective of this study, therefore , is to compare the transcriptome of HERV - W of individuals with MS in time to recurrence with the expression profile of healthy individuals .Twenty blood samples will be collected, ten from individuals with MS in terms of recurrence ( GMS ) and ten from healthy individuals ( GC ) which will be submitted to trascriptome ( RNAseq ) by Ion Proton platform . For analysis of transcripts HERV sequences will be used as reference and sequences of genes responsible for the expression of proinflammatory and anti -inflammatory properties. The analysis of sequences obtained by RNAseq be performed with the help of programs Geneious and CLC Genomics Workbench 5 . In addition , plasma levels of these cytokines will also be measured so that we can establish a relationship between activity /repression of genes associated and plasma levels.