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

• Grant number: 13/24223-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2014
• Effective date (End): February 28, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal researcher: Camila Malta Romano
• Grantee: Luiz Henrique da Silva Nali
• Home Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NALI, LUIZ H.; OLIVAL, GUILHERME S.; SOUSA, FRANCIELLE T. G.; DE OLIVEIRA, ANA CAROLINA S.; MONTENEGRO, HORACIO; DA SILVA, ISRAEL T.; DIAS-NETO, EMAMNUEL; NAYA, HUGO; SPANGENBERG, LUCIA; PENALVA-DE-OLIVEIRA, AUGUSTO C.; et al. Whole transcriptome analysis of multiple Sclerosis patients reveals active inflammatory profile in relapsing patients and downregulation of neurological repair pathways in secondary progressive cases. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 44, SEP 2020. (13/24223-9, 15/05958-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NALI, Luiz Henrique da Silva. Profile of human endogenous retroviruses W family expression in Multiple Sclerosis patients. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) São Paulo.