Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorOLIVAL, Guilherme S. do
dc.contributor.authorFARIA, Thiago S.
dc.contributor.authorNALI, Luiz H. S.
dc.contributor.authorOLIVEIRA, Augusto C. P. de
dc.contributor.authorCASSEB, Jorge
dc.contributor.authorVIDAL, Jose E.
dc.contributor.authorCAVENAGHI, Vitor B.
dc.contributor.authorTILBERY, Charles P.
dc.contributor.authorMORAES, Lenira
dc.contributor.authorFINK, Maria C. S.
dc.contributor.authorSUMITA, Laura M.
dc.contributor.authorPERRON, Herve
dc.contributor.authorROMANO, Camila M.
dc.date.accessioned2014-04-25T22:03:01Z
dc.date.available2014-04-25T22:03:01Z
dc.date.issued2013
dc.description.abstractHuman endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.
dc.description.indexPubMed
dc.description.sponsorshipFAPESP [2010/10619-0]
dc.identifier.citationFRONTIERS IN MICROBIOLOGY, v.4, article ID 172, 7p, 2013
dc.identifier.doi10.3389/fmicb.2013.00172
dc.identifier.issn1664-302X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/5235
dc.language.isoeng
dc.publisherFRONTIERS RESEARCH FOUNDATION
dc.relation.ispartofFrontiers in Microbiology
dc.rightsopenAccess
dc.rights.holderCopyright FRONTIERS RESEARCH FOUNDATION
dc.subjectmultiple sclerosis
dc.subjectimmunopathogeny
dc.subjectendogenous retroviruses
dc.subjectERVWE2
dc.subjectgenetic association
dc.subjectMOG
dc.subject.otherplacental expression
dc.subject.otherherv-w
dc.subject.otherdisease
dc.subject.otherfamily
dc.subject.otherenv
dc.subject.otherretroelements
dc.subject.otherparticles
dc.subject.othersequences
dc.subject.otherpromoter
dc.subject.otherblood
dc.subject.wosMicrobiology
dc.titleGenomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countrySuíça
hcfmusp.affiliation.countryisoch
hcfmusp.author.externalOLIVAL, Guilherme S. do:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
hcfmusp.author.externalFARIA, Thiago S.:Univ Sao Paulo, Inst Med Trop Sao Paulo, Dept Molestias Infecc & Parasitarias LIMHC, BR-05403000 Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, BR-05403000 Sao Paulo, Brazil
hcfmusp.author.externalOLIVEIRA, Augusto C. P. de:Inst Infectol Emilio Ribas, Dept Neurol, Sao Paulo, Brazil
hcfmusp.author.externalVIDAL, Jose E.:Inst Infectol Emilio Ribas, Dept Neurol, Sao Paulo, Brazil
hcfmusp.author.externalCAVENAGHI, Vitor B.:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
hcfmusp.author.externalTILBERY, Charles P.:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
hcfmusp.author.externalMORAES, Lenira:Univ Sao Paulo, Fac Med, Hosp Clin, Dept Neurol, BR-05403000 Sao Paulo, Brazil
hcfmusp.author.externalPERRON, Herve:Univ Sao Paulo, Fac Med, BR-05403000 Sao Paulo, Brazil; Geneuro, Geneva, Switzerland
hcfmusp.citation.scopus26
hcfmusp.contributor.author-fmusphcLUIZ HENRIQUE DA SILVA NALI
hcfmusp.contributor.author-fmusphcJORGE SIMAO DO ROSARIO CASSEB
hcfmusp.contributor.author-fmusphcMARIA CRISTINA DOMINGUES DA SILVA FINK
hcfmusp.contributor.author-fmusphcLAURA MASAMI SUMITA
hcfmusp.contributor.author-fmusphcCAMILA MALTA ROMANO
hcfmusp.description.articlenumber172
hcfmusp.description.volume4
hcfmusp.origemWOS
hcfmusp.origem.pubmed23805135
hcfmusp.origem.scopus2-s2.0-84884220242
hcfmusp.origem.wosWOS:000331180800001
hcfmusp.publisher.cityLAUSANNE
hcfmusp.publisher.countrySWITZERLAND
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